Mitochondrial Heterogeneity in Metabolic Diseases

SIMPLE SUMMARY: Often times mitochondria within a single cell are depicted as homogenous entities both morphologically and functionally. In normal and diseased states, mitochondria are heterogeneous and display distinct functional properties. In both cases, mitochondria exhibit differences in morphology, membrane potential, and mitochondrial calcium levels. However, the degree of heterogeneity is different during disease; or rather, heterogeneity at the physiological state stems from physically distinct mitochondrial subpopulations. Overall, mitochondrial heterogeneity is both beneficial and detrimental to the cellular system; protective in enabling cellular adaptation to biological stress or detrimental in inhibiting protective mechanisms. ABSTRACT: Mitochondria have distinct architectural features and biochemical functions consistent with cell-specific bioenergetic needs. However, as imaging and isolation techniques advance, heterogeneity amongst mitochondria has been observed to occur within the same cell. Moreover, mitochondrial heterogeneity is associated with functional differences in metabolic signaling, fuel utilization, and triglyceride synthesis. These phenotypic associations suggest that mitochondrial subpopulations and heterogeneity influence the risk of metabolic diseases. This review examines the current literature regarding mitochondrial heterogeneity in the pancreatic beta-cell and renal proximal tubules as they exist in the pathological and physiological states; specifically, pathological states of glucolipotoxicity, progression of type 2 diabetes, and kidney diseases. Emphasis will be placed on the benefits of balancing mitochondrial heterogeneity and how the disruption of balancing heterogeneity leads to impaired tissue function and disease onset.