Format

Send to

Choose Destination
See comment in PubMed Commons below
Life Sci. 2013 Sep 3;93(8):313-22. doi: 10.1016/j.lfs.2013.07.005. Epub 2013 Jul 17.

Evaluation of the cardiolipin biosynthetic pathway and its interactions in the diabetic heart.

Author information

1
West Virginia University School of Medicine, Division of Exercise Physiology, Center for Cardiovascular and Respiratory Sciences, Morgantown, WV 26506, USA.

Abstract

AIMS:

We have previously reported alterations in cardiolipin content and inner mitochondrial membrane (IMM) proteomic make-up specifically in interfibrillar mitochondria (IFM) in the type 1 diabetic heart; however, the mechanism underlying this alteration is unknown. The goal of this study was to determine how the cardiolipin biosynthetic pathway and cardiolipin-IMM protein interactions are impacted by type 1 diabetes mellitus.

MAIN METHODS:

Male FVB mice were made diabetic by multiple low-dose streptozotocin injections and sacrificed five weeks post-diabetic onset. Messenger RNA was measured and cardiac mitochondrial subpopulations were isolated. Further mitochondrial functional experimentation included evaluating the protein expression of the enzymes directly responsible for cardiolipin biosynthesis, as well as ATP synthase activity. Interactions between cardiolipin and ATP synthase subunits were also examined.

KEY FINDINGS:

Western blot analysis revealed a significant decrease in cardiolipin synthase (CRLS) protein content in diabetic IFM, with a concomitant decrease in its activity. ATP synthase activity was also significantly decreased. We identified two novel direct interactions between two subunits of the ATP synthase F0 complex (ATP5F1 and ATP5H), both of which were significantly decreased in diabetic IFM.

SIGNIFICANCE:

Overall, these results indicate that type 1 diabetes mellitus negatively impacts the cardiolipin biosynthetic pathway specifically at CRLS, contributing to decreased cardiolipin content and loss of interactions with key ATP synthase F0 complex constituents in the IFM.

KEYWORDS:

ATP synthase; Cardiolipin; Diabetes mellitus; Inner mitochondria membrane; Mitochondria

PMID:
23872101
PMCID:
PMC3805107
DOI:
10.1016/j.lfs.2013.07.005
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center