Furthermore, we believe that the physiological contribution of metabolic reprogramming due to COX7A2L-regulated supercomplex formation has major implications for human disease, not only because glutaminolysis drives the growth of cancer and the development of degenerative diseases 51, 67 but also because succinate accumulation due to supercomplex assembly or COX7A2L expression is an endogenous mitochondrial signal that initiates pathways involved in multiple processes such as adipose tissue thermogenesis and carcinogenesis 68, 69. This evidence concerns the gene COX7A2L and neurodegenerative disease.