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Figure 3. Changes to mitochondrial activity, behavior, and function common to failing myocardium and muscle tissue in sarcopenia. Mitochondria carry out a wide breadth of essential functions in the heart and muscle, and nearly all of these functions are dysregulated in heart failure and sarcopenia. Changes along the electron transport chain (Complexes I-IV and ATP synthase) lead to reduced ATP generation and increase superoxide release. Fuel utilization shifts from predominately fatty acids to alternative fuels, including glucose. Mitochondrial DNAs (mtDNAs) are damaged and released, leading to reduced mitochondrial biogenesis and activation of the innate immune response. Similarly, mitochondrial damage-associated molecular patterns (DAMPs) are exposed, triggering an immune response. Mitochondrial dynamics, including fission and fusion of established mitochondria, are altered, and reduced protein quality control can cause proteostatic stress in the cell.