Mitochondrial energetics and insulin resistance

Abstract

Obesity, insulin resistance, type 2 diabetes mellitus, and aging are associated with impaired skeletal muscle oxidation capacity, reduced mitochondrial content, and lower rates of oxidative phosphorylation. Several studies have reported ultrastructural abnormalities in mitochondrial morphology and reductions in mitochondrial mass in insulin-resistant individuals. From lower organisms to rodents, mitochondrial membrane structure, function, and programmed cell death are regulated in part by the balance between the opposing forces of mitochondrial fusion and fission, suggesting they may also play an important role in human physiology.

Figure 1

Model for mitochondrial fusion/fission in mammalian cells. Mitochondria can undergo constriction and division (1). These events are mediated by the cytosolic Drp1, which bonds and localizes to the constriction site via an interaction with the receptor (anchor)-like protein human Fis1 (hFis1) (2). During fusion, a tether of the MFN-1 or -2 to collateral mitochondrial MFN-1 and -2 conjoins the outer membranes. OPA1, an inner membrane GTPase protein facilitates the fusion of the inner membrane, cristae formation, and unifying of compartments.