Gravitational and mechanical forces shape mitochondrial translation

Life on Earth has evolved in a form suitable for the gravitational force. Although the pivotal role of gravity in gene expression has been suggested, the molecular details remain unclear. Here, we show that mitochondria utilize gravity to activate protein synthesis within the organelle. Genome-wide ribosome profiling reveals reduced mitochondrial translation in mammalian cells and Caenorhabditis elegans under microgravity. We found that attenuation of cell adhesion through laminin-integrin interactions caused the phenotype. Mitochondrial translation is activated by a signal relayed by FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins in the cytosol, and the mitochondrial fatty acid synthesis (mtFAS) pathway in the matrix. Consumption of mitochondrial malonyl-CoA by mtFAS reduces the malonylation of the translational machinery and accelerates the rates of translational initiation and elongation. Physiologically, this system operates in mechano-response of skeletal muscles. Our work provides mechanistic insights into how cells convert gravitational and mechanical forces into translation in mitochondria.