Heme Oxygenase-1 Supports Mitochondrial Energy Production and Electron Transport Chain Activity in Cultured Lung Epithelial Cells

International Journal of Molecular Sciences

David Garcia¹  AbigailL. Peterson²  JenniferF. Carr²  PhyllisA. Dennery²  Alejandro Scaffa³  AndrewJ. Ghio⁴ 

[1] Department of Chemistry, Brown University, Providence, RI 02906, USA;Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02906, USA;Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02906, USA;National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC 27599, USA;

关键词: metabolism;    succinate dehydrogenase;    iron;    heme;   

DOI  :  10.3390/ijms21186941

来源: DOAJ

【 摘 要 】

Heme oxygenase-1 is induced by many cellular stressors and catalyzes the breakdown of heme to generate carbon monoxide and bilirubin, which confer cytoprotection. The role of HO-1 likely extends beyond the simple production of antioxidants, for example HO-1 activity has also been implicated in metabolism, but this function remains unclear. Here we used an HO-1 knockout lung cell line to further define the contribution of HO-1 to cellular metabolism. We found that knockout cells exhibit reduced growth and mitochondrial respiration, measured by oxygen consumption rate. Specifically, we found that HO-1 contributed to electron transport chain activity and utilization of certain mitochondrial fuels. Loss of HO-1 had no effect on intracellular non-heme iron concentration or on proteins whose levels and activities depend on available iron. We show that HO-1 supports essential functions of mitochondria, which highlights the protective effects of HO-1 in diverse pathologies and tissue types. Our results suggest that regulation of heme may be an equally significant role of HO-1.

【 授权许可】

Unknown