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Mitochondria are highly dynamic and communicative organelles that regulate a variety of cellular processes including energy homeostasis, redox status, thermogenesis and cell death via apoptosis. Mitochondria collaborate with a host of intracellular organelles including endoplasmic reticulum, peroxisomes, lysosomes and nuclei to maintain metabolic homeostasis. Mitochondrial dysfunction disrupts metabolism and is thought to underlie cellular aging as well as the development of chronic diseases such as type 2 diabetes, cardiovascular disease, heart failure and aging-associated sarcopenia. Since mitochondria are enriched in cardiac and striated skeletal muscle, and since these tissues are critical in regulating whole body metabolism, insulin action, and locomotion, the objective of this conference is to identify novel mechanisms controlling mitochondrial function and connect mitochondrial phenotypes with improved health and disease pathobiology. New insight into the biology and pathobiology of mitochondria will allow for the advance of therapeutic approaches that can be utilized to combat metabolic-related diseases associated with mitochondrial dysfunction. The ongoing convergence of the fields of muscle metabolism and mitochondrial biology since our understanding of the precise molecular signaling that links mitochondrial function (biogenesis, fission-fusion-mitophagy dynamics, and mitochondrial genome integrity) with integrative metabolism and muscle action remains inadequate. These deficiencies in our fundamental knowledge of mitochondrial biology and the implications of this knowledge gap in the treatment and clinical care of common and rare mitochondrial diseases underpin the importance of this Keystone Symposia conference. Moreover, opportunities for interdisciplinary interactions will be further enhanced by the joint conference on “Mitochondria in Aging and Age-related Pathology.” This conference will bring together investigators from diverse areas of integrative biology and metabolism who typically do not interact or attend the same research symposia, sparking the development of new collaborations, novel biological concepts and innovative therapeutic strategies to harness the mitochondria for metabolic disease prevention.