Основні поняття
Mitochondrial protein FAM210A is essential for maintaining mitochondrial integrity and metabolism, which in turn regulates cytosolic protein translation and muscle growth.
Анотація
The study investigates the role of the mitochondrial protein FAM210A in regulating skeletal muscle growth and homeostasis. Key highlights:
FAM210A expression is positively correlated with muscle mass in mice and humans. Muscle-specific deletion of Fam210a in mice leads to progressive muscle atrophy, weakness, and premature death.
Fam210a knockout disrupts mitochondrial cristae structure, reduces mitochondrial density and function, and reverses the TCA cycle towards the reductive direction, resulting in acetyl-CoA accumulation.
The increased acetyl-CoA causes hyperacetylation of cytosolic ribosomal proteins, leading to ribosomal disassembly and translational defects. Transplantation of Fam210a-null mitochondria into wildtype myoblasts is sufficient to induce protein hyperacetylation.
The study reveals a novel crosstalk between mitochondria and ribosomes mediated by FAM210A, which is essential for maintaining muscle protein synthesis and growth.
Статистика
Fam210a mRNA level is reduced by 37% in old vs young human skeletal muscle.
Fam210a mRNA level is reduced by 33% in vastus lateralis muscle after 48 hours of knee immobilization.
Fam210a mRNA level is reduced by 18.6% in Pompe disease patients and 42% in Duchenne Muscular Dystrophy patients compared to healthy controls.
Fam210a mRNA level is increased by 21.5% in myostatin knockout mouse muscle.
Цитати
"Skeletal muscle growth and hypertrophy are contributed by the accretion of myonuclei from differentiated muscle stem cells (satellite cells) at early stages and by protein synthesis in the existing myofibers after the myonuclei addition ceases."
"Understanding the mechanisms that regulate muscle growth provides potential strategies to boost muscle health for the improvement of life qualities."
"These results uncover a novel role of FAM210A in regulating mitochondria metabolism and provide evidence linking metabolic inputs to the regulation of skeletal muscle growth and atrophy through protein acetylation."