“…When activated in response to energetic stress, such as exercise, degradation through mitophagy occurs in spatially distinct domains (Glancy et al, 2017;Laker et al, 2017;Drake et al, 2021), suggesting autophagosomes and lysosomes may be synthesized in the vicinity of the mitochondrial region identified for degradation. Recent discoveries have suggested that the spatial specificity of mitophagy may be governed through locally distinct mechanisms at mitochondria, possibly in response to the energetic microenvironment (Miyamoto et al, 2015;Glancy et al, 2017;Zong et al, 2019;Drake et al, 2021;Schmitt et al, 2022). In this review, we briefly summarize the production of cellular energy by mitochondria and the biochemical and molecular consequences of energetic stress, namely acute exercise, in relation to mechanisms that locally monitor mitochondrial energetics to promote mitophagy and identify unresolved questions.…”