Pub Date : 2025-08-28DOI: 10.1016/j.cophys.2025.100849
Vidhi M Shah , Rosalie C Sears
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an 8% five-year survival rate. KRAS, the major oncogenic driver, triggers several phosphorylation cascades, making phosphatases, particularly protein phosphatase 2A (PP2A), which accounts for 50–70% of cellular phosphatase activity, a critical regulator. Through association with multiple regulatory subunits, PP2A modulates both tumor-suppressive and tumor-promoting functions. The tumor-suppressive function is often inhibited in PDAC by endogenous inhibitors like SET and CIP2A, which are frequently upregulated. This review examines the multifaceted roles of PP2A in PDAC, with a focus on its published roles in KRAS-MYC signaling, DNA damage response, and epithelial-to-mesenchymal transition, as well as current and emerging therapeutic strategies aimed at modulating PP2A activity.
{"title":"Protein phosphatase 2A as a therapeutic target in pancreatic cancer: past insights, recent advances, and future directions","authors":"Vidhi M Shah , Rosalie C Sears","doi":"10.1016/j.cophys.2025.100849","DOIUrl":"10.1016/j.cophys.2025.100849","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an 8% five-year survival rate. KRAS, the major oncogenic driver, triggers several phosphorylation cascades, making phosphatases, particularly protein phosphatase 2A (PP2A), which accounts for 50–70% of cellular phosphatase activity, a critical regulator. Through association with multiple regulatory subunits, PP2A modulates both tumor-suppressive and tumor-promoting functions. The tumor-suppressive function is often inhibited in PDAC by endogenous inhibitors like SET and CIP2A, which are frequently upregulated. This review examines the multifaceted roles of PP2A in PDAC, with a focus on its published roles in KRAS-MYC signaling, DNA damage response, and epithelial-to-mesenchymal transition, as well as current and emerging therapeutic strategies aimed at modulating PP2A activity.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"46 ","pages":"Article 100849"},"PeriodicalIF":1.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-08DOI: 10.1016/j.cophys.2025.100848
Diego Quiroga , Rachel Daniel , Samarjit Das
MicroRNAs (miRNAs) are essential post-transcriptional regulators of gene expression, and accumulating evidence supports their presence and function within mitochondria. These mitochondrial microRNAs (MitomiRs) modulate key processes such as oxidative phosphorylation, ATP production, calcium homeostasis, and reactive oxygen species balance in cardiac tissue. Despite growing recognition of their importance, the mechanisms governing miRNA trafficking to mitochondria remain incompletely understood. This review explores the current knowledge on miRNA biogenesis, mitochondrial import pathways — including the roles of Argonaute 2 (AGO2), the Translocase of the Outer/Inner Mitochondrial Membrane (TOM/TIM) complexes, and Polynucleotide Phosphorylase (PNPase) — and the regulatory impact of specific MitomiRs, such as miR-181c, miR-210, miR-378, let-7b, and miR-1. Understanding how these molecules influence mitochondrial function provides insight into their therapeutic potential in cardiovascular disease.
{"title":"Mechanisms of microRNA trafficking to mitochondria in the heart","authors":"Diego Quiroga , Rachel Daniel , Samarjit Das","doi":"10.1016/j.cophys.2025.100848","DOIUrl":"10.1016/j.cophys.2025.100848","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are essential post-transcriptional regulators of gene expression, and accumulating evidence supports their presence and function within mitochondria. These mitochondrial microRNAs (MitomiRs) modulate key processes such as oxidative phosphorylation, ATP production, calcium homeostasis, and reactive oxygen species balance in cardiac tissue. Despite growing recognition of their importance, the mechanisms governing miRNA trafficking to mitochondria remain incompletely understood. This review explores the current knowledge on miRNA biogenesis, mitochondrial import pathways — including the roles of Argonaute 2 (AGO2), the Translocase of the Outer/Inner Mitochondrial Membrane (TOM/TIM) complexes, and Polynucleotide Phosphorylase (PNPase) — and the regulatory impact of specific MitomiRs, such as miR-181c, miR-210, miR-378, let-7b, and miR-1. Understanding how these molecules influence mitochondrial function provides insight into their therapeutic potential in cardiovascular disease.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100848"},"PeriodicalIF":1.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-30DOI: 10.1016/j.cophys.2025.100847
Arpita Ghosh Mitra
In the human genome, most transcribed RNA does not translate into protein, yet it plays a crucial role in gene expression regulation. This ‘dark matter of the genome’ is called noncoding RNAs (ncRNAs), which are involved in the pathogenesis of different diseases, viz., cancer. According to the length of nucleotides, ncRNAs are categorised into long ncRNAs (lncRNAs) or small ncRNAs. Recent emerging studies are exploring the massive role of ncRNAs behind pathophysiology and the scope of utilising these huge segments as diagnostic and prognostic indicators, as well as therapeutic targets of cancer. This brief and succinct review will focus on recent publications on the status and major contribution of ncRNAs in cancer, ranging from pathogenesis and diagnosis to prognosis and therapy.
{"title":"Noncoding RNA in cancer: pathogenesis to therapeutic targets","authors":"Arpita Ghosh Mitra","doi":"10.1016/j.cophys.2025.100847","DOIUrl":"10.1016/j.cophys.2025.100847","url":null,"abstract":"<div><div>In the human genome, most transcribed RNA does not translate into protein, yet it plays a crucial role in gene expression regulation. This ‘dark matter of the genome’ is called noncoding RNAs (ncRNAs), which are involved in the pathogenesis of different diseases, viz., cancer. According to the length of nucleotides, ncRNAs are categorised into long ncRNAs (lncRNAs) or small ncRNAs. Recent emerging studies are exploring the massive role of ncRNAs behind pathophysiology and the scope of utilising these huge segments as diagnostic and prognostic indicators, as well as therapeutic targets of cancer. This brief and succinct review will focus on recent publications on the status and major contribution of ncRNAs in cancer, ranging from pathogenesis and diagnosis to prognosis and therapy.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100847"},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-02DOI: 10.1016/j.cophys.2025.100836
Matthew Lloyd , Brooke A Prakash , Lucy Zhao, Guohao Ni, Yining Ru, Sridhar R Vasudevan
Circadian rhythms orchestrate metabolism and brain function, aligning internal physiological processes with the 24-hour day–night cycle. Growing evidence highlights a reciprocal relationship between circadian regulation, metabolism, and neurobiological processes. Circadian disruption impairs glucose and lipid homeostasis, alters neurotransmitter and endocrine signalling, and triggers stress response, forming a feedback loop that impacts metabolism and brain function. These disturbances are implicated in many conditions, such as obesity, diabetes, depression, and bipolar disorder. This review examines recent advances in the interplay between circadian regulation, metabolism, and mental health, emphasising shared molecular mechanisms and their role in disease progression. Understanding these connections may ultimately inform therapeutic strategies that integrate circadian-based approaches to improve treatments for metabolic and psychiatric disorders.
{"title":"Circadian rhythms in metabolism and mental health: a reciprocal regulatory network with implications for metabolic and neuropsychiatric disorders","authors":"Matthew Lloyd , Brooke A Prakash , Lucy Zhao, Guohao Ni, Yining Ru, Sridhar R Vasudevan","doi":"10.1016/j.cophys.2025.100836","DOIUrl":"10.1016/j.cophys.2025.100836","url":null,"abstract":"<div><div>Circadian rhythms orchestrate metabolism and brain function, aligning internal physiological processes with the 24-hour day–night cycle. Growing evidence highlights a reciprocal relationship between circadian regulation, metabolism, and neurobiological processes. Circadian disruption impairs glucose and lipid homeostasis, alters neurotransmitter and endocrine signalling, and triggers stress response, forming a feedback loop that impacts metabolism and brain function. These disturbances are implicated in many conditions, such as obesity, diabetes, depression, and bipolar disorder. This review examines recent advances in the interplay between circadian regulation, metabolism, and mental health, emphasising shared molecular mechanisms and their role in disease progression. Understanding these connections may ultimately inform therapeutic strategies that integrate circadian-based approaches to improve treatments for metabolic and psychiatric disorders.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100836"},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-30DOI: 10.1016/j.cophys.2025.100834
Georgios K Paschos, Ronan Lordan, Garret A FitzGerald
The circadian clock aligns behavior and physiology with environmental rhythms, and its disruption has been associated with increased risk of metabolic and neurological diseases. This review examines the emerging trends and mounting evidence demonstrating that there are sex-specific differences in circadian physiology relevant to health. Preclinical and clinical studies indicate that females exhibit greater circadian resilience, robust transcriptional rhythms, and resistance to clock perturbation compared to males. These influences affect susceptibility to metabolic conditions and responses to circadian perturbations like shift work. Notably, sex differences in response to alcohol consumption and cancer chronotherapy have emerged as fields of significant interest. Future research must consider both sexes to refine existing interventions and uncover the complex mechanisms of circadian physiology for more inclusive therapeutic strategies.
{"title":"Intersection of sex and circadian biology","authors":"Georgios K Paschos, Ronan Lordan, Garret A FitzGerald","doi":"10.1016/j.cophys.2025.100834","DOIUrl":"10.1016/j.cophys.2025.100834","url":null,"abstract":"<div><div>The circadian clock aligns behavior and physiology with environmental rhythms, and its disruption has been associated with increased risk of metabolic and neurological diseases. This review examines the emerging trends and mounting evidence demonstrating that there are sex-specific differences in circadian physiology relevant to health. Preclinical and clinical studies indicate that females exhibit greater circadian resilience, robust transcriptional rhythms, and resistance to clock perturbation compared to males. These influences affect susceptibility to metabolic conditions and responses to circadian perturbations like shift work. Notably, sex differences in response to alcohol consumption and cancer chronotherapy have emerged as fields of significant interest. Future research must consider both sexes to refine existing interventions and uncover the complex mechanisms of circadian physiology for more inclusive therapeutic strategies.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100834"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-27DOI: 10.1016/j.cophys.2025.100837
Jeffrey J Kelu
The circadian clock synchronises biological processes with environmental cues, optimising fitness and energy efficiency. Among these, cell growth regulation is a critical yet underexplored area. While primarily linked to rhythmic cell division, cell growth also arises from the cyclic accumulation of cellular components driving volume expansion. This review highlights advances in understanding how the circadian clock regulates the synthesis and degradation of key cellular constituents, particularly RNAs and proteins, in both homeostatic and growing cells. These processes are essential for maintaining cellular homeostasis and supporting tissue development and regeneration. Further exploration of circadian turnover and its integration with cellular growth pathways could pave the way for chronotherapeutic strategies.
{"title":"Circadian control of cellular constituent turnover and growth","authors":"Jeffrey J Kelu","doi":"10.1016/j.cophys.2025.100837","DOIUrl":"10.1016/j.cophys.2025.100837","url":null,"abstract":"<div><div>The circadian clock synchronises biological processes with environmental cues, optimising fitness and energy efficiency. Among these, cell growth regulation is a critical yet underexplored area. While primarily linked to rhythmic cell division, cell growth also arises from the cyclic accumulation of cellular components driving volume expansion. This review highlights advances in understanding how the circadian clock regulates the synthesis and degradation of key cellular constituents, particularly RNAs and proteins, in both homeostatic and growing cells. These processes are essential for maintaining cellular homeostasis and supporting tissue development and regeneration. Further exploration of circadian turnover and its integration with cellular growth pathways could pave the way for chronotherapeutic strategies.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100837"},"PeriodicalIF":2.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-26DOI: 10.1016/j.cophys.2025.100833
Samantha Le Sommer , Maria I Kontaridis
Autoimmune and autoinflammatory diseases are a diverse group of disorders that stem from aberrant immune responses against self. While autoimmune disorders are characterized by lymphocyte-driven antigen-specific responses, autoinflammatory diseases are driven by chronic activation of the innate immune system. However, to date, both groups of disorders lack clear understanding for their onset and the functional mechanisms conducive to their pathology and have few efficacious, safe, and/or curative treatment options for patients. The SH2 domain–containing protein tyrosine phosphatase (SHP2), the protein encoded by the PTPN11 gene, is a nodal enzyme involved in embryogenesis, development, proliferation, differentiation, and survival of cells. Mutations in PTPN11 are associated with the development of congenital disorders as well as several types of cancers. Recently, links between autoimmunity and genetic developmental disorders have also revealed a key role for SHP2 activity in autoimmune–autoinflammatory pathophysiology. Its association with these disorders has begun to unravel the molecular mechanisms that contribute to the onset of autoimmunity. In this review, we will discuss the emergent role of SHP2 in autoimmunity and the current known and unknown molecular mechanisms of its regulation in these processes and propose the translational impact it may have as a therapeutic in the near future.
{"title":"SHP2 happens, just sail with it: the role of the protein tyrosine phosphatase SHP2 in autoimmune and autoinflammatory diseases","authors":"Samantha Le Sommer , Maria I Kontaridis","doi":"10.1016/j.cophys.2025.100833","DOIUrl":"10.1016/j.cophys.2025.100833","url":null,"abstract":"<div><div>Autoimmune and autoinflammatory diseases are a diverse group of disorders that stem from aberrant immune responses against self. While autoimmune disorders are characterized by lymphocyte-driven antigen-specific responses, autoinflammatory diseases are driven by chronic activation of the innate immune system. However, to date, both groups of disorders lack clear understanding for their onset and the functional mechanisms conducive to their pathology and have few efficacious, safe, and/or curative treatment options for patients. The SH2 domain–containing protein tyrosine phosphatase (SHP2), the protein encoded by the <em>PTPN11</em> gene, is a nodal enzyme involved in embryogenesis, development, proliferation, differentiation, and survival of cells. Mutations in <em>PTPN11</em> are associated with the development of congenital disorders as well as several types of cancers. Recently, links between autoimmunity and genetic developmental disorders have also revealed a key role for SHP2 activity in autoimmune–autoinflammatory pathophysiology. Its association with these disorders has begun to unravel the molecular mechanisms that contribute to the onset of autoimmunity. In this review, we will discuss the emergent role of SHP2 in autoimmunity and the current known and unknown molecular mechanisms of its regulation in these processes and propose the translational impact it may have as a therapeutic in the near future.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100833"},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-24DOI: 10.1016/j.cophys.2025.100835
Andrea Ciorciari , Katja A Lamia
Circadian rhythms, regulated by central and peripheral clocks, shape physiological processes through clock gene activity and external cues, modulating metabolic pathways, hormonal regulation, and body temperature. By acting on these factors, exercise serves as a powerful zeitgeber, impacting the timing of biological functions. This review highlights insights from molecular to behavioral aspects, examining exercise's role in addressing circadian disruptions, its therapeutic potential for metabolic, psychiatric, and cancer-related conditions, and its applications in enhancing physical performance. Exercise Chronophysiology emerges as a promising integrative approach, offering innovative strategies for promoting health, preventing disease, and optimizing athletic performance.
{"title":"From clock genes to exercise: shaping the field of Exercise Chronophysiology","authors":"Andrea Ciorciari , Katja A Lamia","doi":"10.1016/j.cophys.2025.100835","DOIUrl":"10.1016/j.cophys.2025.100835","url":null,"abstract":"<div><div>Circadian rhythms, regulated by central and peripheral clocks, shape physiological processes through clock gene activity and external cues, modulating metabolic pathways, hormonal regulation, and body temperature. By acting on these factors, exercise serves as a powerful zeitgeber, impacting the timing of biological functions. This review highlights insights from molecular to behavioral aspects, examining exercise's role in addressing circadian disruptions, its therapeutic potential for metabolic, psychiatric, and cancer-related conditions, and its applications in enhancing physical performance. Exercise Chronophysiology emerges as a promising integrative approach, offering innovative strategies for promoting health, preventing disease, and optimizing athletic performance.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100835"},"PeriodicalIF":2.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obesity is a growing problem worldwide, with its pathophysiology being keenly explored. Previously, the noncoding transcriptome was considered transcriptional noise with no functional relevance. However, emerging evidence suggests a critical role for noncoding RNAs, especially long noncoding RNAs (lncRNAs), in obesity. Several lncRNAs have been identified that facilitate the development of obesity (such as LINK-A) or resist obesity (such as lnc266). These findings emphasize the importance of the study of lncRNA, which could be the master regulators of disease progression and the key to the development of novel therapeutics.
{"title":"Role of lncRNAs in pathophysiology of obesity","authors":"Vikram Krishnappa Shettigar, Venkata Naga Srikanth Garikipati","doi":"10.1016/j.cophys.2025.100832","DOIUrl":"10.1016/j.cophys.2025.100832","url":null,"abstract":"<div><div>Obesity is a growing problem worldwide, with its pathophysiology being keenly explored. Previously, the noncoding transcriptome was considered transcriptional noise with no functional relevance. However, emerging evidence suggests a critical role for noncoding RNAs, especially long noncoding RNAs (lncRNAs), in obesity. Several lncRNAs have been identified that facilitate the development of obesity (such as <em>LINK-A)</em> or resist obesity (such as lnc266). These findings emphasize the importance of the study of lncRNA, which could be the master regulators of disease progression and the key to the development of novel therapeutics.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"44 ","pages":"Article 100832"},"PeriodicalIF":2.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-08DOI: 10.1016/j.cophys.2025.100831
Sidhant Khatri, Anna Blumental-Perry
The mitochondrion contains its own genome that encodes subunits of respiratory complexes, components of the translation machinery, and numerous noncoding RNAs (ncRNAs). Some of these ncRNAs are antisense transcripts of their respective genes, regulating their maturation within mitochondria. Others facilitate mitochondria-to-nucleus communication, conveying mitochondrial status to the nucleus and coordinating synergy between the genomes. The first known mito-ncRNAs that exit mitochondria were those generated from the control regions of the mitochondrial genome. Recent evidence suggests that this phenomenon is broader, encompassing multiple mitochondrial sense and antisense transcripts and mito-tRNAs. mito-ncRNAs are regulated by the proliferative state of the cell, physiological stresses, and viral infections. Both within and outside the organelle, mito-ncRNAs serve as scaffolds for protein complex assembly, as modulators of promoter occupancy, heterochromatin states, nucleolar functions, and spliceosome selectivity, and as precursors and regulators of miRNA networks. Here, we summarize and discuss current knowledge regarding mito-ncRNA-mediated signaling pathways.
{"title":"Mitochondrial ncRNAs beyond the mitochondrion: coordinators of organelle crosstalk","authors":"Sidhant Khatri, Anna Blumental-Perry","doi":"10.1016/j.cophys.2025.100831","DOIUrl":"10.1016/j.cophys.2025.100831","url":null,"abstract":"<div><div>The mitochondrion contains its own genome that encodes subunits of respiratory complexes, components of the translation machinery, and numerous noncoding RNAs (ncRNAs). Some of these ncRNAs are antisense transcripts of their respective genes, regulating their maturation within mitochondria. Others facilitate mitochondria-to-nucleus communication, conveying mitochondrial status to the nucleus and coordinating synergy between the genomes. The first known mito-ncRNAs that exit mitochondria were those generated from the control regions of the mitochondrial genome. Recent evidence suggests that this phenomenon is broader, encompassing multiple mitochondrial sense and antisense transcripts and mito-tRNAs. mito-ncRNAs are regulated by the proliferative state of the cell, physiological stresses, and viral infections. Both within and outside the organelle, mito-ncRNAs serve as scaffolds for protein complex assembly, as modulators of promoter occupancy, heterochromatin states, nucleolar functions, and spliceosome selectivity, and as precursors and regulators of miRNA networks. Here, we summarize and discuss current knowledge regarding mito-ncRNA-mediated signaling pathways.</div></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":"45 ","pages":"Article 100831"},"PeriodicalIF":2.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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