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FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse.

ABSTRACT: Mitochondria are not only essential for energy production in eukaryocytes but also a key regulator of intracellular signaling. Here, we report an unappreciated role of mitochondria in regulating cytosolic protein translation in skeletal muscle cells (myofibers). We show that the expression of mitochondrial protein FAM210A (Family With Sequence Similarity 210 Member A) is positively associated with muscle mass in mice and humans. Muscle-specific Myl1^Cre-driven Fam210a knockout (Fam210a^MKO) in mice reduces mitochondrial density and function, leading to progressive muscle atrophy and premature death. Metabolomic and biochemical analyses reveal that Fam210a^MKO reverses the oxidative TCA cycle towards the reductive direction, resulting in acetyl-CoA accumulation and hyperacetylation of cytosolic proteins. Specifically, hyperacetylation of several ribosomal proteins leads to disassembly of ribosomes and translational defects. Transplantation of Fam210a^MKO mitochondria into wildtype myoblasts is sufficient to elevate protein acetylation in recipient cells. These findings reveal a novel crosstalk between the mitochondrion and ribosome mediated by FAM210A.

SUBMITTER: Chen J

PROVIDER: S-EPMC10418219 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse.

Chen Jingjuan J Yue Feng F Kim Kun Ho KH Zhu Peipei P Qiu Jiamin J Tao W Andy WA Kuang Shihuan S

bioRxiv : the preprint server for biology 20230805

Mitochondria are not only essential for energy production in eukaryocytes but also a key regulator of intracellular signaling. Here, we report an unappreciated role of mitochondria in regulating cytosolic protein translation in skeletal muscle cells (myofibers). We show that the expression of mitochondrial protein FAM210A (Family With Sequence Similarity 210 Member A) is positively associated with muscle mass in mice and humans. Muscle-specific Myl1Cre-driven Fam210a< ...[more]

PMID: 37577696

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FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse.

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FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse.

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