Lipidomic characterization of streptozotocin-induced heart mitochondrial dysfunction

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Rita Ferreira (Author) Other; Gabriela Guerra (Author) Other; Ana Isabel Padrao (Author) Other; Tania Melo (Author) Other; Rui Vitorino (Author) Other; Jose Alberto Duarte (Author) FADEUP; Fernando Remiao (Author) FFUP; Pedro Domingues (Author) Other; Francisco Amado (Author) Other; Rosario Domingues, MR (Author) Other

Journal

Title: Mitochondrion

Vol. 13

Pages: 762-771

ISSN: 1567-7249

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 25 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-006-JQV

DOI: 10.1016/j.mito.2013.05.001

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10