Pub Date : 2022-08-25DOI: 10.1093/lifemeta/loac019
Shaoqun Zhou, Yongshuo Ma, Y. Shang, X. Qi, Sanwen Huang, Jiayang Li
Plants are talented biochemists that produce a broad diversity of small molecules. These so-called specialized metabolites play critical roles in the adaptive evolution of plants to defend against biotic and abiotic stresses, attract pollinators, and modulate soil microbiota for their own benefits. Many plant specialized metabolites have been used as nutrition and flavor compounds in our daily food, as well as drugs for treatment of human diseases. Current multi-omics tools have significantly accelerated the process of biosynthetic pathway elucidation in plants through correlation analyses, genetic mapping, and de novo biosynthetic gene cluster predictions. Understanding the biosynthesis of plant specialized metabolites has enabled reconstitution of naturally-occurring specialized metabolic pathways in microbial hosts, providing a sustainable supply of these high-value molecules. In this review, we illustrate the general functions of several typical plant specialized metabolites in natural ecosystems and for human societies. We then provide an overview of current methods elucidating the biosynthetic pathways of plant specialized metabolites, and synthetic biology strategies that optimize the efficiency of heterologous biosynthetic pathways in microbial hosts. Moving forward, dissection of the functions and application of plant specialized metabolites by using current multidiscipline approaches would greatly benefit to the scientific community and human societies.
{"title":"Functional diversity and metabolic engineering of plant specialized metabolites","authors":"Shaoqun Zhou, Yongshuo Ma, Y. Shang, X. Qi, Sanwen Huang, Jiayang Li","doi":"10.1093/lifemeta/loac019","DOIUrl":"https://doi.org/10.1093/lifemeta/loac019","url":null,"abstract":"\u0000 Plants are talented biochemists that produce a broad diversity of small molecules. These so-called specialized metabolites play critical roles in the adaptive evolution of plants to defend against biotic and abiotic stresses, attract pollinators, and modulate soil microbiota for their own benefits. Many plant specialized metabolites have been used as nutrition and flavor compounds in our daily food, as well as drugs for treatment of human diseases. Current multi-omics tools have significantly accelerated the process of biosynthetic pathway elucidation in plants through correlation analyses, genetic mapping, and de novo biosynthetic gene cluster predictions. Understanding the biosynthesis of plant specialized metabolites has enabled reconstitution of naturally-occurring specialized metabolic pathways in microbial hosts, providing a sustainable supply of these high-value molecules. In this review, we illustrate the general functions of several typical plant specialized metabolites in natural ecosystems and for human societies. We then provide an overview of current methods elucidating the biosynthetic pathways of plant specialized metabolites, and synthetic biology strategies that optimize the efficiency of heterologous biosynthetic pathways in microbial hosts. Moving forward, dissection of the functions and application of plant specialized metabolites by using current multidiscipline approaches would greatly benefit to the scientific community and human societies.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47444542","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}
Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum. Reactive oxygen species (ROS) elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles, while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing (POA), which might be related to the activation of cellular endogenous antioxidant system. All these defects could be rescued by ketone body administration, which suppressed ROS-activated follicle apoptosis. Our results suggest that the internal metabolic homeostasis of new-born mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.
{"title":"The neonatal ketone body is important for primordial follicle pool formation and regulates ovarian ageing in mice","authors":"Xin-ying Wang, Xin-Ge Zhang, Yong-Juan Sang, Danyang Chong, X. Sheng, Haiquan Wang, Chao-Fan Yang, Gui Jun Yan, Haixiang Sun, Chao-Jun Li","doi":"10.1093/lifemeta/loac017","DOIUrl":"https://doi.org/10.1093/lifemeta/loac017","url":null,"abstract":"\u0000 Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum. Reactive oxygen species (ROS) elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles, while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing (POA), which might be related to the activation of cellular endogenous antioxidant system. All these defects could be rescued by ketone body administration, which suppressed ROS-activated follicle apoptosis. Our results suggest that the internal metabolic homeostasis of new-born mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44521752","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 : 2022-08-04DOI: 10.1093/lifemeta/loac015
Fucheng Dong, Wei Li
{"title":"α-ketoglutaric acid: a new chance for male fertility preservation","authors":"Fucheng Dong, Wei Li","doi":"10.1093/lifemeta/loac015","DOIUrl":"https://doi.org/10.1093/lifemeta/loac015","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45320261","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 : 2022-08-01DOI: 10.1093/lifemeta/loac014
Qian Shi, Duane D Hall, Long-Sheng Song
In a recent study published in Life Metabolism, Quan et al. reported that intracellular Ca2+ dysregulation in cardiomyocyte can be both a cause and an effect of cardiac insulin resistance that ultimately leads to diabetic cardiomyopathy.
{"title":"A Ca<sup>2+</sup> cycling defect connects insulin resistance and heart failure.","authors":"Qian Shi, Duane D Hall, Long-Sheng Song","doi":"10.1093/lifemeta/loac014","DOIUrl":"https://doi.org/10.1093/lifemeta/loac014","url":null,"abstract":"<p><p>In a recent study published in <i>Life Metabolism</i>, Quan <i>et al</i>. reported that intracellular Ca<sup>2+</sup> dysregulation in cardiomyocyte can be both a cause and an effect of cardiac insulin resistance that ultimately leads to diabetic cardiomyopathy.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-28DOI: 10.1093/lifemeta/loac013
Chao Quan, Sangsang Zhu, Rui-Tao Wang, Jiamou Chen, Qiaoli Chen, Min Li, Shu-Yi Su, Q. Du, Minjun Liu, Hong-Yu Wang, Shuai Chen
Diabetic cardiomyopathy (DCM) is currently a progressive and non-stoppable complication in type 2 diabetic patients. Metabolic insults and insulin resistance are involved in its pathogenesis; however, the underlying mechanisms are still not clearly understood. Here we show that calcium dysregulation can be both a cause and a consequence of cardiac insulin resistance that leads to DCM. A western diet (WD) induces the development of DCM through at least three phases in mice, among which an early phase depends on impaired Thr 484-phosphorylation of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) elicited by insulin resistance. Mutation of SERCA2a-Thr 484 to a non-phosphorylatable alanine delays calcium re-uptake into the sarcoplasmic reticulum (SR) in the cardiomyocytes and decreases cardiac function at the baseline. Importantly, this mutation blunts the early phase of DCM, but has no effect on disease progression in the following phases. Interestingly, impairment of SR calcium re-uptake caused by the SERCA2a-Thr 484 mutation inhibited processing of insulin receptor precursor through FURIN convertase, resulting in cardiac insulin resistance. Collectively, these data reveal a bidirectional relationship between insulin resistance and impairment of calcium homeostasis, which may underlie the early pathogenesis of DCM. Our findings have therapeutic implications for early intervention of DCM.
{"title":"Impaired SERCA2a phosphorylation causes diabetic cardiomyopathy through impinging on cardiac contractility and precursor protein processing","authors":"Chao Quan, Sangsang Zhu, Rui-Tao Wang, Jiamou Chen, Qiaoli Chen, Min Li, Shu-Yi Su, Q. Du, Minjun Liu, Hong-Yu Wang, Shuai Chen","doi":"10.1093/lifemeta/loac013","DOIUrl":"https://doi.org/10.1093/lifemeta/loac013","url":null,"abstract":"\u0000 Diabetic cardiomyopathy (DCM) is currently a progressive and non-stoppable complication in type 2 diabetic patients. Metabolic insults and insulin resistance are involved in its pathogenesis; however, the underlying mechanisms are still not clearly understood. Here we show that calcium dysregulation can be both a cause and a consequence of cardiac insulin resistance that leads to DCM. A western diet (WD) induces the development of DCM through at least three phases in mice, among which an early phase depends on impaired Thr 484-phosphorylation of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) elicited by insulin resistance. Mutation of SERCA2a-Thr 484 to a non-phosphorylatable alanine delays calcium re-uptake into the sarcoplasmic reticulum (SR) in the cardiomyocytes and decreases cardiac function at the baseline. Importantly, this mutation blunts the early phase of DCM, but has no effect on disease progression in the following phases. Interestingly, impairment of SR calcium re-uptake caused by the SERCA2a-Thr 484 mutation inhibited processing of insulin receptor precursor through FURIN convertase, resulting in cardiac insulin resistance. Collectively, these data reveal a bidirectional relationship between insulin resistance and impairment of calcium homeostasis, which may underlie the early pathogenesis of DCM. Our findings have therapeutic implications for early intervention of DCM.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48808216","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 : 2022-07-14DOI: 10.1093/lifemeta/loac012
Chang Xu, Yexian Yuan, Cha Zhang, Yuchuan Zhou, Jinping Yang, Huadong Yi, Ishwari Gyawali, Jingyi Lu, Sile Guo, Yunru Ji, Chengquan Tan, Songbo Wang, Yongliang Zhang, Q. Jiang, G. Shu
Infertility is a global concern attributed to genetic defects, lifestyle, nutrition, and any other factors that affect the local metabolism and niche microenvironment of the reproductive system. 2-oxoglutarate receptor 1 (OXGR1) is abundantly expressed in the testis; however, its cellular distribution and biological function of OXGR1 in the male reproductive system remain unclear. In the current study, we demonstrated that OXGR1 is primarily expressed in epididymal smooth muscle cells (SMCs). Aging and heat stress significantly reduced OXGR1 expression in the epididymis. Using OXGR1 global knockout and epididymal-specific OXGR1 knockdown models, we revealed that OXGR1 is essential for epididymal sperm maturation and fluid acid-base balance. Supplementation of α-ketoglutaric acid (AKG), the endogenous ligand of OXGR1, effectively reversed epididymal sperm maturation disorders caused by aging and heat stress. Furthermore, in vitro studies showed that AKG markedly stimulated the release of instantaneous intracellular calcium from epididymal SMCs and substantially reduced the pHi value in the epididymal SMCs via OXGR1. Mechanistically, we discovered that AKG/OXGR1 considerably increased the expression of Na +/HCO3− cotransporter (NBCe1) mRNA in the epididymal SMCs, mediated by intracellular calcium signaling. The local AKG/OXGR1 system changed the epididymal fluid pH value and HCO3− concentration, thereby regulating sperm maturation via intracellular calcium signaling and NBCe1 mRNA expression. This studyfor the first time reveals the crucial role of OXGR1 in male fertility and sheds light on the applicability of metabolic intermediates in the nutritional intervention of reproduction.
{"title":"Smooth muscle AKG/OXGR1 signaling regulates epididymal fluid acid-base balance and sperm maturation","authors":"Chang Xu, Yexian Yuan, Cha Zhang, Yuchuan Zhou, Jinping Yang, Huadong Yi, Ishwari Gyawali, Jingyi Lu, Sile Guo, Yunru Ji, Chengquan Tan, Songbo Wang, Yongliang Zhang, Q. Jiang, G. Shu","doi":"10.1093/lifemeta/loac012","DOIUrl":"https://doi.org/10.1093/lifemeta/loac012","url":null,"abstract":"\u0000 Infertility is a global concern attributed to genetic defects, lifestyle, nutrition, and any other factors that affect the local metabolism and niche microenvironment of the reproductive system. 2-oxoglutarate receptor 1 (OXGR1) is abundantly expressed in the testis; however, its cellular distribution and biological function of OXGR1 in the male reproductive system remain unclear. In the current study, we demonstrated that OXGR1 is primarily expressed in epididymal smooth muscle cells (SMCs). Aging and heat stress significantly reduced OXGR1 expression in the epididymis. Using OXGR1 global knockout and epididymal-specific OXGR1 knockdown models, we revealed that OXGR1 is essential for epididymal sperm maturation and fluid acid-base balance. Supplementation of α-ketoglutaric acid (AKG), the endogenous ligand of OXGR1, effectively reversed epididymal sperm maturation disorders caused by aging and heat stress. Furthermore, in vitro studies showed that AKG markedly stimulated the release of instantaneous intracellular calcium from epididymal SMCs and substantially reduced the pHi value in the epididymal SMCs via OXGR1. Mechanistically, we discovered that AKG/OXGR1 considerably increased the expression of Na +/HCO3− cotransporter (NBCe1) mRNA in the epididymal SMCs, mediated by intracellular calcium signaling. The local AKG/OXGR1 system changed the epididymal fluid pH value and HCO3− concentration, thereby regulating sperm maturation via intracellular calcium signaling and NBCe1 mRNA expression. This studyfor the first time reveals the crucial role of OXGR1 in male fertility and sheds light on the applicability of metabolic intermediates in the nutritional intervention of reproduction.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48401287","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 : 2022-07-07DOI: 10.1093/lifemeta/loac011
Hui Chen, Y. Tao, Min-Dian Li, Yuxuan Gu, Jiaxi Yang, You Wu, Dongmei Yu, Changzheng Yuan
To our knowledge, this study is one of the few population-based studies that explore the association of TPEI and cognitive decline, although accumulating studies have linked TPEI to health outcomes, including obesity [8], hypertension [9], and cardiovascular health [10]. Emerging studies suggested that meal timing is associated with cognitive function. An experimental study showed that evenly spreading the same amount of energy into four meals can improve short-term cognitive performance than that of two meals [11]. Another meta-analysis [12] including 34 experimental studies showed that breakfast skipping is related to worse acute cognitive function among healthy adults than breakfast consumers. Our findings were generally consistent with prior evidence, showing that breakfast skipping was associated with exceptionally faster cognitive decline than other TPEIs, corroborated by the secondary finding that higher energy intakes in the morning were associated with better cognitive function and slower decline. For snack intake, we observed that only snacks consumed after dinner exhibited a potentially beneficial role, most likely resulting from the fact that people who consumed snacks at night usually used to be brain workers with higher education levels and tended to have a better cognitive function. Our findings should be placed in the context of China's rapid transitions in eating habits, where accessibility of food choices as snacks may vary significantly across populations. In conclusion, we observed that maintaining balanced energy intake across three major meals was associated with significantly better cognitive function than the other five unevenly-distributed patterns. In particular, breakfast skipping was associated with significantly worse cognitive function and faster cognitive decline over time. The observed associations were similar across major prespecified subgroups. Further studies are needed to confirm our findings in different populations and reveal the underlying mechanisms. If proven causal, these findings will add to the evidence for future public health recommendations on balanced temporal pattern of energy intake for primary prevention of cognitive decline in the aging population.
{"title":"Temporal patterns of energy intake and cognitive function and its decline: a community-based cohort study in China","authors":"Hui Chen, Y. Tao, Min-Dian Li, Yuxuan Gu, Jiaxi Yang, You Wu, Dongmei Yu, Changzheng Yuan","doi":"10.1093/lifemeta/loac011","DOIUrl":"https://doi.org/10.1093/lifemeta/loac011","url":null,"abstract":"To our knowledge, this study is one of the few population-based studies that explore the association of TPEI and cognitive decline, although accumulating studies have linked TPEI to health outcomes, including obesity [8], hypertension [9], and cardiovascular health [10]. Emerging studies suggested that meal timing is associated with cognitive function. An experimental study showed that evenly spreading the same amount of energy into four meals can improve short-term cognitive performance than that of two meals [11]. Another meta-analysis [12] including 34 experimental studies showed that breakfast skipping is related to worse acute cognitive function among healthy adults than breakfast consumers. Our findings were generally consistent with prior evidence, showing that breakfast skipping was associated with exceptionally faster cognitive decline than other TPEIs, corroborated by the secondary finding that higher energy intakes in the morning were associated with better cognitive function and slower decline. For snack intake, we observed that only snacks consumed after dinner exhibited a potentially beneficial role, most likely resulting from the fact that people who consumed snacks at night usually used to be brain workers with higher education levels and tended to have a better cognitive function. Our findings should be placed in the context of China's rapid transitions in eating habits, where accessibility of food choices as snacks may vary significantly across populations. In conclusion, we observed that maintaining balanced energy intake across three major meals was associated with significantly better cognitive function than the other five unevenly-distributed patterns. In particular, breakfast skipping was associated with significantly worse cognitive function and faster cognitive decline over time. The observed associations were similar across major prespecified subgroups. Further studies are needed to confirm our findings in different populations and reveal the underlying mechanisms. If proven causal, these findings will add to the evidence for future public health recommendations on balanced temporal pattern of energy intake for primary prevention of cognitive decline in the aging population.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42951323","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 : 2022-07-01DOI: 10.1093/lifemeta/loac010
Camille Allard, D. Cota
{"title":"Paracrine actions of GLP1 in the gut unraveled","authors":"Camille Allard, D. Cota","doi":"10.1093/lifemeta/loac010","DOIUrl":"https://doi.org/10.1093/lifemeta/loac010","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609311","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 : 2022-06-24DOI: 10.1093/lifemeta/loac009
P. Xia, Liankui Zhou, Jialiang Guan, Wanqiu Ding, Y. Liu
Animals respond to mitochondrial perturbation by activating the mitochondrial unfolded protein response (UPR mt) to induce the transcription of mitochondrial stress response genes. In C. elegans, activation of UPR mt allows the animals to maintain organismal homeostasis, activate the innate immune response and promote lifespan extension. Here we show that splicing factors such as PRP-19 are required for the induction of UPR mt in C. elegans. PRP-19 also modulates mitochondrial perturbation-induced innate immune response and lifespan extension. Knockdown of PRP-19 in mammalian cells suppresses UPR mt activation and disrupts the mitochondrial network. These findings reveal an evolutionarily conserved mechanism that maintains mitochondrial homeostasis and controls innate immunity and lifespan through splicing factors.
{"title":"Splicing factor PRP-19 regulates mitochondrial stress response","authors":"P. Xia, Liankui Zhou, Jialiang Guan, Wanqiu Ding, Y. Liu","doi":"10.1093/lifemeta/loac009","DOIUrl":"https://doi.org/10.1093/lifemeta/loac009","url":null,"abstract":"\u0000 Animals respond to mitochondrial perturbation by activating the mitochondrial unfolded protein response (UPR mt) to induce the transcription of mitochondrial stress response genes. In C. elegans, activation of UPR mt allows the animals to maintain organismal homeostasis, activate the innate immune response and promote lifespan extension. Here we show that splicing factors such as PRP-19 are required for the induction of UPR mt in C. elegans. PRP-19 also modulates mitochondrial perturbation-induced innate immune response and lifespan extension. Knockdown of PRP-19 in mammalian cells suppresses UPR mt activation and disrupts the mitochondrial network. These findings reveal an evolutionarily conserved mechanism that maintains mitochondrial homeostasis and controls innate immunity and lifespan through splicing factors.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45995843","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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