Huettemann 2015 Abstract MiP2015
|Regulation of mitochondrial respiration and apoptosis by cytochrome c phosphorylation.|
Huettemann M (2015)
Mammalian cytochrome c (Cytc) is a small globular protein and functions as a mobile electron carrier between complexes III and IV of the electron transport chain (ETC). In addition, Cytc participates in type II apoptosis, during which it is released from the mitochondria. Considering the key role of Cytc in cell life and death, it can be expected to be tightly regulated. We have previously shown that cell signaling pathways target mitochondrial proteins including Cytc, which is phosphorylated on two distinct tyrosine residues in heart and liver. We show here by mass spectrometry that Cytc isolated from mammalian kidney tissue is phosphorylated on a novel residue, threonine 28. To functionally study this phosphorylation we used in vivo-phosphorylated Cytc and phoshomimetic Thr28Glu Cytc. The latter replacement leads to a reduction of the Cytc redox potential and a partial inhibition of respiration, or ‘controlled respiration’ in the reaction with cytochrome c oxidase compared to unphosphorylated wild-type Cytc. These results fit our model that under healthy conditions ETC proteins are phosphorylated to limit electron flux in the electron transport chain, which in turn prevents a hyperpolarization of the mitochondrial membrane potential, a known cause of reactive oxygen species (ROS) production and trigger of apoptosis.
Labels: Pathology: Obesity Stress:Cell death
Enzyme: Complex IV;cytochrome c oxidase
Event: C1, Poster MiP2015
Center Mol Med Genetics, Wayne State Univ, Detroit, MI, USA. - email@example.com
This work was supported by the U.S. National Inst Health grant GM089900.