Cytochrome-c levels in subsarcolemmal and interfibrillar mitochondria of cardiomyocytes of normal and failing canine hearts

Document Type

Conference Proceeding

Publication Date

7-8-2025

Publication Title

Eur J Heart Fail

Keywords

Cardiovascular System & Cardiology

Abstract

Background: Cytochrome c (Cyt-c) is an electron carrier hemeprotein located in large amounts on the inner mitochondrial (MITO) membrane and plays a key role in MITO respiration and cell apoptosis. By transferring electrons from MITO complex III to complex IV, Cyt-c facilitates cell ATP energy production. Cyt-c release from MITO to the cytosol is a key factor in cardiomyocyte apoptosis. Two primary subpopulations of MITO namely, subsarcolemmal MITO (SSM) and interfibrillar MITO (IFM) are present in cardiomyocytes. IFM are organized in parallel rows between contractile myofilaments and primarily provide ATP for contraction and relaxation. SSM generate ATP for a variety of cell surface processes including cell signaling and ion exchange. We showed that MITO function is abnormal in HF with increased cytosolic Cyt-c in cardiomyocytes. This study examined the expression of Cyt-c in SSM and IFM of left ventricular (LV) cardiomyocytes of normal (NL) dogs and dogs with chronic HF (LVEF <35%) produced by intracoronary microembolizations. Methods: Studies were performed using LV tissue from 8 NL and 8 HF dogs. Cyt-c protein levels were determined by Western blotting in the lysate of SSM and IFM isolated from approximately 1 gram of fresh LV tissue. Results were normalized to porin, a MITO protein that is unchanged in HF. All band intensities were quantified in densitometric units (du). Results: Porin protein levels were similar in NL vs. HF SSM and IFM. In NL dogs, Cyt-c protein levels were nearly 3-fold higher in IFM compared to SSM (6.03 ± 0.44 vs. 2.17 ± 0.54, p < 0.05). Cyt-c protein levels were reduced nearly 5-fold in SSM from HF compared to NL dogs (0.15 ± 0.04 vs. 0.79 ± 0.21, p < 0.05) and nearly 2-fold in IFM from HF compared to NL dogs (1.48 ± 0.26 vs. 2.38 ± 0.29, p < 0.05). Conclusion: The results indicate that IFM in NL cardiomyocytes contain higher levels of Cyt-c compared to SSM, perhaps to account for the higher ATP demands of muscle contraction and relaxation. Cyt-c levels are reduced in both SSM and IFM of failing cardiomyocytes compared to NL, likely contributing to the state of energy deprivation in HF and consistent with previous observations of increased levels of cytosolic Cyt-c and activation of programmed cell death.

Volume

27

First Page

46

Last Page

47

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