Abstract
Myocardial mitochondria dysfunction seems to represent an important pathogenic factor underlying cardiomyopathy, a common complication of type 1 diabetes mellitus (T1DM). Despite significant progress in the understanding of the molecular mechanisms of mitochondrial function in the heart, the interplay between phospholipids and membrane proteins of this organelle is still poorly comprehended. Using a well-characterized animal model of T1DM obtained by the administration of streptozotocin, phospholipid profiling of isolated mitochondria was performed using MS-based approaches, which was analyzed together with oxidative phosphorylation (OXPHOS) complexes activities and their susceptibility to oxidation, and the expression of cytochrome c, the uncoupling protein UCP-3 and the mitochondrial transcription factor Tfam. Although in higher amounts, mitochondria from T1DM heart presented lower OXPHOS activity and lower transcription ability. This profile was related to phospholipid (PL) remodeling characterized by higher phosphatidylcholine levels, lower phosphatidylglycerol, phosphatidylinositol and sphingomyelin content, higher amounts of long fatty acyl side chains and increased lipid peroxidation, particularly of cardiolipin (CL). CL peroxidation was paralleled by lower cytochrome c content. Though in higher levels, UCP-3 does not seem to protect heart mitochondrial PL and membrane proteins from the oxidative damage induced by four weeks of hyperglycemia. Taken together, our data suggest that PL remodeling of heart mitochondria is an early event in T1DM pathogenesis and is related with OXPHOS dysfunction.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
