Mitochondrial Communications最新文献

Exercise is potent stimulus for mitochondrial adaptations, serving to activate mitochondrial biogenesis as well as mitochondrial turnover. Through the process of mitophagy, dysfunctional mitochondria are selectively targeted and recycled via the lysosomes, which is activated following a single bout of exercise. The microphthalamia (MiT) family of transcription factors, including TFEB and TFE3, are widely recognized as the master regulators of lysosomal biogenesis, as they homo- and hetero-dimerize to transcriptionally regulate lysosomal and macroautophagy-related genes. It is currently unknown to what extent TFEB and TFE3 regulate mitophagy, and whether these transcription factors mediate mitochondrial adaptations to contractile activity (CA). Here we show that following an acute bout of contractile activity in cultured C2C12 murine skeletal muscle myotubes, LC3-II mitophagy flux is induced and the absence of TFEB or TFE3 impairs this acute mitophagic response. However, the loss of either transcription factor alone does not mitigate the improvements in oxygen consumption seen following chronic contractile activity (CCA). Chronic contractile activity also elicited functional improvements in lysosomes including a reduction in size and increased proteolytic activity, evidenced by increased digestion and unquenching of DQ-BSA fluorophore, thereby illustrating a level of redundancy between the two transcription factors in mediating chronic contractile activity-induced adaptations. However, in the absence of both TFEB and TFE3, lysosomal adaptations were not observed following chronic contractile activity and subsequent mitochondrial adaptations were attenuated. These findings underscore the importance of the lysosomes, and of TFEB and TFE3, in mediating mitochondrial adaptations to chronic contractile activity.

Mitochondrial dynamics are closely related to various cellular physiological activities, including cell proliferation, homeostasis, and cell migration, and are regulated by a variety of enzymes, proteins and cytokines. Abnormal mitochondrial dynamics have been identified in multiple diseases, such as Charcot-Marie-Tooth type 2A, Parkinson's disease, Alzheimer's disease and cancer. A small fraction of these diseases can be treated by targeting drugs that correct unbalanced mitochondrial dynamics. Further in-depth research into mitochondrial dynamics is significant to helping us better understand the pathogenesis of these diseases, leading to the development of targeted drugs to halt the progression of the disease and even cure it completely. In this review, we discuss primary aspects of mitochondrial dynamics, alterations in mitochondrial dynamics under stress, and abnormities in mitochondrial dynamics that promote diseases. We look forward to exploring the regulation of mitochondrial dynamics, which will provide new ideas for treating those diseases in the future.

Optic Atrophy 1 (OPA1), a mitochondrial inner protein, is involved in both mitochondrial fusion dynamic and cell apoptosis. OPA1 Exon4b (OPA1-Exon4b) was reported to be downregulated in hepatocellular carcinoma (HCC). However, the relationship between OPA1-Exon4b and HCC remains unclear. Here we demonstrated that OPA1-Exon4b is related with migration using genome-wide transcriptome profiling. OPA1-Exon4b overexpression suppresses the migration and invasion, and cellular ATP production in HCC cells. The inhibition of migration and invasion by OPA1-Exon4b overexpression could be rescued by ATP addition, showing that OPA1-Exon4b suppresses the migration and invasion by decreasing ATP. We further demonstrated OPA1 overexpression induces the enlargement of mtDNA nucleoids in HCC cells. Thus, our study demonstrated a key role of OPA1-Exon4b to regulate the migration and invasion in HCC, which could provide a new prospect for the clinical diagnosis and therapy of HCC.

Mitochondria are important organelles of eukaryotic cells and involved in a variety of cellular processes including oxidative phosphorylation for generating ATP, apoptosis, steroid synthesis, and signal transduction. Mitochondrion contains double membranes, which are mainly composed of phospholipids. Although mitochondria can synthesize some of phospholipids, most of phospholipids are biosynthesized in the endoplasmic reticulum (ER). ER-mitochondria contacts are required for the transfer of some phospholipids, which are critical for mitochondrial phospholipids metabolism, membrane organization and functions. In this review, we will focus on the synthesis, metabolism and function of mitochondrial phospholipids and the role of mitochondria in lipid metabolism. Additionally, we will discuss the connection between mitochondrial phospholipids disorder and human diseases.