Assessing Multiple Features of Mitochondrial Function

Alterations of energy metabolism are key features of insulin resistance, diabetes, and diabetes-related complications. However, the role of mitochondria—the cell’s power plants—in abnormal metabolism is less certain. Mitochondria are responsible for oxidative phosphorylation, which couples substrate oxidation to synthesize ATP. Essentially, the reduction of dinucleotides enables electrons to transfer via the electron transport system across the inner mitochondrial membrane. Energy released from electron transfer is used for proton transport into the matrix, thereby establishing an electrochemical proton gradient (ΔΨ) (1). Mitochondrial function involves various features, each of which can be examined by different methods. The use of different approaches to assess mitochondrial function, coupled with imprecise terminology regarding “mitochondrial dysfunction” can lead to confusing data interpretation. Several studies have reported lower mitochondrial function expressed per muscle mass in type 2 diabetes as assessed by enzyme activities (2,3) or by high-resolution respirometry (4–7). Although reduced mitochondrial content could serve as explanation for this observation (3,5,8), some studies have also noted lower intrinsic function (4,6,7,9)—that is, reduced respiratory capacity per mitochondrion. Mitochondrial production of reactive oxygen species (ROS) also leads to the formation of lipid peroxides. In turn, these can induce oxidative stress thereby causing cellular and mitochondrial damage (10,11). In this context, it is of interest to simultaneously monitor ΔΨ, ATP, and ROS production in a single tissue sample. In this issue of Diabetes , Yu et al. (12) describe a method for evaluating the physiology of isolated mitochondria. They used 2-deoxyglucose …