Mechanisms of mitochondrial respiratory adaptation

Mitochondrial energetic adaptations encompass a plethora of conserved processes that maintain cell and organismal fitness and survival in the changing environment by adjusting the respiratory capacity of mitochondria. These mitochondrial responses are governed by general principles of regulatory biology exemplified by changes in gene expression, protein translation, protein complex formation, transmembrane transport, enzymatic activities and metabolite levels. These changes can promote mitochondrial biogenesis and membrane dynamics that in turn support mitochondrial respiration. The main regulatory components of mitochondrial energetic adaptation include: the transcription coactivator peroxisome proliferator-activated receptor-gamma (PPAR gamma) coactivator 1 alpha (PGC1 alpha) and associated transcription factors; mTOR and endoplasmic reticulum stress signalling; TOM70-dependent mitochondrial protein import; the cristae remodelling factors, including mitochondrial contact site and cristae organizing system (MICOS) and OPA1; lipid remodelling; and the assembly and metabolite-dependent regulation of respiratory complexes. These adaptive molecular and structural mechanisms increase respiration to maintain basic processes specific to cell types and tissues. Failure to execute these regulatory responses causes cell damage and inflammation or senescence, compromising cell survival and the ability to adapt to energetically demanding conditions. Thus, mitochondrial adaptive cellular processes are important for physiological responses, including to nutrient availability, temperature and physical activity, and their failure leads to diseases associated with mitochondrial dysfunction such as metabolic and age-associated diseases and cancer. Mitochondrial respiratory function needs to adapt to the energetic demands of the cell. These adaptive responses encompass transcriptional, translational and post-translational mechanisms that together enable regulation of respiratory chain assembly and mitochondrial membrane remodelling to fine-tune energy generation in accordance with intracellular and extracellular cues.

Automated summary

Mitochondrial energetic adaptations are a series of processes that help cells and organisms adapt to changing environments by adjusting the respiratory capacity of mitochondria. These adaptations are regulated by general principles of regulatory biology and are important for maintaining cell survival and adapting to demanding conditions. Failure to execute these adaptations can lead to cell damage, inflammation, and diseases such as metabolic disorders, age-related diseases, and cancer.