Mitochondrial Heterogeneity is More Important than “Biogenesis”——The Causes,Risks and Scientific Paradigms of Exercise-Induced Mitochondrial Biogenesis

Exercise can induce mitochondrial biogenesis in multiple organs and tissues, so the “exercise promotes mitochondrial biogenesis through XXX to prevent or improve XXX disease” has become a conventional scientific paradigm. This paradigm guides our interpretation of existing data and scientific hypothesis for the future. With the application of single-cell gene sequencing, more and more evidence showed that the emphasis on “mitochondrial biogenesis” may overlook the heterogeneity between individuals of mitochondria. The opinon of “exercise-induced mitochondrial biogenesis” as a health benefit often contradicts the interpretation of complex pathology, because mitochondrial biogenesis also have “side effects”, and exercise-activated signaling is involved in diseases progression as well. This review proposes a paradigm based on experimental and evolutionary evidence: mitochondrial biogenesis induced by exercise is the only choice of cells in response to increased oxygen uptake, but it is not necessarily in improving diseases. In gene-deficient or specific pathological models, exercise promotes heterogeneous or incomplete mitochondrial biogenesis to resist increased oxygen pressure. The matching of mitochondrial phenotype, distribution and intracellular ATP requirement is more important than increased number of mitochondrial. The regulation of mitochondrial heterogeneity by exercise and the relationship between mitochondria should be paid more attention.