The Role of Membrane Protein ATAD3A in The Mitochondrial Quality Control / 生物化学与生物物理进展

Mitochondrial quality control plays an important role in maintaining homeostasis of mitochondrial network and normal function of mitochondria. ATPase family AAA domain-containing protein 3A (ATAD3A) is one of the mitochondrial membrane proteins involved in the regulation of mitochondrial structure and function, mitochondrial dynamics, mitophagy and other important biological processes. Recent studies show that ATAD3A not only interacts with Mic60/Mitofilin and mitochondrial transcription factor A (TFAM) to maintain mitochondrial cristae morphology and oxidative phosphorylation, but also interacts with dynamin-related protein 1 (Drp1) to positively/negatively regulate mitochondrial fission. In addition, ATAD3A serves as a bridging factor between the translocase of the outer mitochondrial membrane (TOM) complex and translocase of the inner mitochondrial membrane (TIM) complex to facilitate the import of PTEN-induced putative kinase protein 1 (PINK1) into mitochondria and its processing displays a pro-autophagic or anti-autophagic activity. This article reviews the role and mechanism of ATAD3A in regulating mitochondrial quality control. Firstly, as an inner mitochondrial membrane protein, ATAD3A is involved in maintaining the stability of mitochondrial crista structure, and its gene deletion or mutation will cause the loss and breakage of crista. Secondly, ATAD3A is also involved in maintaining mitochondrial respiratory function and mitochondrial nucleoid homeostasis, and its gene deletion or mutation can reduce the activity of mitochondrial respiratory chain complex and enhance the size and movement of nucleoid. Thirdly, ATAD3A participates in the negative regulation of mitochondrial fusion, but its role in mitochondrial fission may dependent on specific cell types, as it can promote and/or inhibit the mitochondrial fission by increasing and/or decreasing phosphorylation or oligomerization of Drp1. Finally, ATAD3A can interact with mitophagy-related proteins (e.g. PINK1, autophagy/beclin-1 regulator 1 (AMBRA1), acylglycerol kinase (AGK)) to enhance/reduce PINK1-Parkin-dependent mitophagy.

Advances in the study of mitophagy-related receptor proteins / 生理学报

Cells selectively scavenge redundant or damaged mitochondria by mitophagy, which is an important mechanism of mitochondrial quality control. Recent studies have shown that mitophagy is mainly regulated by autophagy-related genes (Atgs) in yeast cells, while mitochondrial membrane associated proteins such as PTEN-induced putative kinase 1 (PINK1), NIX/BNIP3L, BNIP3, FUN14 domain containing 1 (FUNDC1), FKBP8/FKBP38, Bcl-2-like protein 13 (Bcl2L13), nucleotide binding domain and leucine-rich-repeat-containing proteins X1 (NLRX1), prohibitin 2 (PHB2) and lipids such as cardiolipin (CL) are the key mitophagic receptors in mammalian cells, which can selectively recognize damaged mitochondria, recruit them into isolation membranes by binding to microtubule-associated protein 1 light chain 3 (LC3) or γ-aminobutyric acid receptor-associated protein (GABARAP), and then fuse with lysosomes to eliminate the trapped mitochondria. This article reviews recent research progress of mitophagy-related receptor proteins.

The role and mechanism of leucyl-tRNA synthetase in the regulation of protein synthesis in aging skeletal muscle / 生理学报

The imbalance of protein metabolism is the major cause of skeletal muscle atrophy, and the decrease of protein synthesis directly leads to the occurrence and development of age-related sarcopenia. The canonical role of leucyl-tRNA synthetase (LeuRS) is ligating leucine to the cognate tRNA, and thus it plays a central role in genetic coding. With the further studies of LeuRS in recent years, LeuRS has been found to control protein homeostasis in aging skeletal muscle via its non-canonical role. In this paper, we reviewed the structure and biological features of aminoacyl-tRNA synthetase and LeuRS, and summarized the recent advances in studies on the effects of LeuRS in regulating aging skeletal muscle protein synthesis as an intracellular leucine sensor. Moreover, we also analyzed the potential role of LeuRS in activation of mammalian target of rapamycin complex 1 (mTORC1) signaling transduction pathway in response to anabolic stimuli such as exercise and amino acids ingestion. This paper may provide some new ideas for the prevention, diagnosis and treatment of age-related sarcopenia.