Examination of cardiolipin biosynthesis in the diabetic heart

Abstract

Cardiac complications are a main cause of mortality in diabetic patients. Diabetes mellitus (DM) contributes to mitochondrial dysfunction, with the inner mitochondrial membrane (IMM) being highly affected. The IMM houses both vital processes and an essential lipid environment that contains cardiolipin (CL), which is a phospholipid required for proper mitochondrial function. Two cardiac mitochondrial subpopulations exist: subsarcolemmal (SSM) and interfibrillar (IFM). We previously reported decreased CL content in diabetic IFM, but the mechanisms behind this CL loss are unknown. The goal of this study was to determine how the CL biosynthetic pathway is impacted by type 1 DM. FVB mice were made diabetic by streptozotocin injection. Five weeks post‐diabetic onset, ejection fraction, fractional shortening, and cardiac output were decreased in the diabetic group (*P<0.05 for all three). mRNA content of the CL biosynthetic pathway enzymatic constituents indicated no change between treatment groups. Western blot analysis revealed decreased CL synthase protein content in diabetic IFM, with a concomitant decrease in its activity (*P<0.05 for both). Overall, the results suggest that type 1 DM negatively impacts the CL biosynthetic pathway specifically at CL synthase, and may be a contributing mechanism leading to decreased CL content observed in the diabetic heart.(Supported: NIH‐DP2DK083095, 5T32HL090610)