Faculty Collaboration Database

Substrate-dependent differential regulation of mitochondrial bioenergetics in the heart and kidney cortex and outer medulla. Biochim Biophys Acta Bioenerg 2022 Feb 01;1863(2):148518

Date

12/06/2021

Pubmed ID

34864090

Pubmed Central ID

PMC8957717

DOI

10.1016/j.bbabio.2021.148518

Scopus ID

2-s2.0-85120828118 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

The kinetics and efficiency of mitochondrial oxidative phosphorylation (OxPhos) can depend on the choice of respiratory substrates. Furthermore, potential differences in this substrate dependency among different tissues are not well-understood. Here, we determined the effects of different substrates on the kinetics and efficiency of OxPhos in isolated mitochondria from the heart and kidney cortex and outer medulla (OM) of Sprague-Dawley rats. The substrates were pyruvate+malate, glutamate+malate, palmitoyl-carnitine+malate, alpha-ketoglutarate+malate, and succinate±rotenone at saturating concentrations. The kinetics of OxPhos were interrogated by measuring mitochondrial bioenergetics under different ADP perturbations. Results show that the kinetics and efficiency of OxPhos are highly dependent on the substrates used, and this dependency is distinctly different between heart and kidney. Heart mitochondria showed higher respiratory rates and OxPhos efficiencies for all substrates in comparison to kidney mitochondria. Cortex mitochondria respiratory rates were higher than OM mitochondria, but OM mitochondria OxPhos efficiencies were higher than cortex mitochondria. State 3 respiration was low in heart mitochondria with succinate but increased significantly in the presence of rotenone, unlike kidney mitochondria. Similar differences were observed in mitochondrial membrane potential. Differences in H₂O₂ emission in the presence of succinate±rotenone were observed in heart mitochondria and to a lesser extent in OM mitochondria, but not in cortex mitochondria. Bioenergetics and H₂O₂ emission data with succinate±rotenone indicate that oxaloacetate accumulation and reverse electron transfer may play a more prominent regulatory role in heart mitochondria than kidney mitochondria. These studies provide novel quantitative data demonstrating that the choice of respiratory substrates affects mitochondrial responses in a tissue-specific manner.

Author List

Tomar N, Zhang X, Kandel SM, Sadri S, Yang C, Liang M, Audi SH, Cowley AW Jr, Dash RK

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Hydrogen Peroxide