Hancock 2016 Amino Acids

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Hancock CN, Liu W, Alvord WG, Phang JM (2016) Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate. Amino Acids 48:859-72.

» PMID: 26660760 Open Access

Hancock CN, Liu W, Alvord WG, Phang JM (2016) Amino Acids

Abstract: Proline dehydrogenase/oxidase (PRODH/POX) is a mitochondrial protein critical to multiple stress pathways. Because of the roles of PRODH/POX in signaling, and its shared localization to the mitochondrial inner membrane with the electron transport chain (ETC), we investigated whether there was a direct relationship between PRODH/POX and regulation of the ETC. We found that PRODH/POX binds directly to CoQ1 and that CoQ1-dependent PRODH/POX activity required functional Complex III and Complex IV. PRODH/POX supported respiration in living cells during nutrient stress; however, expression of PRODH/POX resulted in an overall decrease in respiratory fitness. Effects on respiratory fitness were inhibited by DHP and NAC, indicating that these effects were mediated by PRODH/POX-dependent reactive oxygen species (ROS) generation. PRODH/POX expression resulted in a dose-dependent down-regulation of Complexes I-IV of the ETC, and this effect was also mitigated by the addition of DHP and NAC. We found that succinate was an uncompetitive inhibitor of PRODH/POX activity, inhibited ROS generation by PRODH/POX, and alleviated PRODH/POX effects on respiratory fitness. The findings demonstrate novel cross-talk between proline and succinate respiration in vivo and provide mechanistic insights into observations from previous animal studies. Our results suggest a potential regulatory loop between PRODH/POX and succinate in regulation of mitochondrial respiration.

Keywords: Proline Bioblast editor: Gnaiger E

Labels: MiParea: Respiration 

Organism: Mouse  Tissue;cell: Liver  Preparation: Intact cells, Isolated mitochondria, Oxidase;biochemical oxidation 

Coupling state: LEAK, ROUTINE, ET  Pathway: S, Other combinations, ROX 

  • Erratum to: Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate