Mitochondrial translation and coordinated cytosolic translation in metabolic homeostasis and disease

Mitochondria are essential organelles that regulate cellular metabolism, signaling, and stress responses. Their function depends on coordinated protein synthesis from the mitochondrial and nuclear genomes, together with mechanisms that preserve mitochondrial proteostasis. Translation of both nuclear- and mitochondrial-encoded transcripts is dynamically regulated in response to developmental, metabolic, and environmental cues, allowing mitochondria to remodel their proteome and adapt to changing physiological demands. Disruption of these processes impairs respiratory complex assembly, mitochondrial function, and protein homeostasis, contributing to a wide range of metabolic, cardiovascular, muscular, neurodegenerative, and immune disorders. In this review, we summarize the evolutionary specialization of the mitochondrial translational machinery and the molecular mechanisms that regulate mitochondrial protein synthesis. We discuss recent advances in cytosolic translational control of nuclear-encoded mitochondrial proteins, mito-nuclear coordination, tissue-specific regulation of mitochondrial proteostasis, and their implications for human disease. Finally, we highlight emerging challenges and future directions in the translational regulation of mitochondrial protein synthesis and its relevance to mitochondrial biology and disease.