Cytochrome c phosphorylation: Control of mitochondrial electron transport chain flux and apoptosis
| Autor: | Alice A. Turner, Asmita Vaishnav, Jenney Liu, Maurice-Andre Recanati, Maik Hüttemann, Hasini A. Kalpage, Brian F.P. Edwards, Lawrence I. Grossman, Matthew P. Zurek, Antoine Khobeir, Thomas H. Sanderson, Icksoo Lee, Junmei Wan, Lara Hakim, Nabil Yazdi, Paul T. Morse |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death Apoptosis Mitochondrion Biochemistry Article Electron Transport 03 medical and health sciences 0302 clinical medicine Cytochrome c oxidase Humans Phosphorylation Inner mitochondrial membrane chemistry.chemical_classification Reactive oxygen species biology Chemistry Cytochrome c Cytochromes c Cell Biology Electron transport chain Cell biology 030104 developmental biology 030220 oncology & carcinogenesis biology.protein |
| Zdroj: | Int J Biochem Cell Biol |
| Popis: | Cytochrome c (Cytc)(1)is a cellular life and death decision molecule that regulates cellular energy supply and apoptosis through tissue specific post-translational modifications. Cytc is an electron carrier in the mitochondrial electron transport chain (ETC) and thus central for aerobic energy production. Under conditions of cellular stress, Cytc release from the mitochondria is a committing step for apoptosis, leading to apoptosome formation, caspase activation, and cell death. Recently, Cytc was shown to be a target of cellular signaling pathways that regulate the functions of Cytc by tissue-specific phosphorylations. So far five phosphorylations sites of Cytc have been mapped and functionally characterized, Tyr97, Tyr48, Thr28, Ser47, and Thr58. All five phosphorylations partially inhibit respiration, which we propose results in optimal intermediate mitochondrial membrane potentials and low ROS production under normal conditions. Four of the phosphorylations result in inhibition of the apoptotic functions of Cytc, suggesting a cytoprotective role for phosphorylated Cytc. Interestingly, these phosphorylations are lost during stress conditions such as ischemia. This results in maximal ETC flux during reperfusion, mitochondrial membrane potential hyperpolarization, excessive ROS generation, and apoptosis. We here present a new model proposing that the electron transfer from Cytc to cytochrome c oxidase is the rate-limiting step of the ETC, which is regulated via post-translational modifications of Cytc. This regulation may be dysfunctional in disease conditions such as ischemia-reperfusion injury and neurodegenerative disorders through increased ROS, or cancer where post-translational modifications on Cytc may provide a mechanism to evade apoptosis. |
| Databáze: | OpenAIRE |
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