Role of Protein Phosphorylation among Oxidative Phosphorylation Components


Mitochondria are important organelles for cellular physiology considering their role in generation of ATP and reactive oxygen species, calcium homeostasis and programmed cell death. In particular, mitochondria produce ATP via oxidative phosphorylation. Mitochondrial activity must be tightly regulated as alteration to the organelle functions can lead to different pathologies including neurodegenerative and metabolic diseases. Phosphorylation of mitochondrial proteins, including the enzymes involved in oxidative phosphorylation, emerged as an important way to modulate mitochondrial metabolism according to physiological conditions. In recent years, several kinases and phosphatases were observed within mitochondria. Numerous phosphorylation sites among the components of the oxidative phosphorylation machinery were observed. These findings open a new field in mitochondrial physiology and cellular biology, showing that well‚Äźknown signalling pathways can reach proteins within mitochondria to adjust the organelle activity to extramitochondrial stimuli.

Key Concepts

  • Mitochondria provide the most part of ATP used by cells via oxidative phosphorylation.
  • Kinases and phosphatases are present within mitochondria.
  • Intramitochondrial kinases target several components of the oxidative phosphorylation machinery.
  • Phosphorylation of mitochondrial proteins represents an important mean to modulate oxidative phosphorylation and other mitochondrial functions.
  • Better knowledge about translocation of kinases and phosphatases inside mitochondria is needed.

Keywords: mitochondria; oxidative phosphorylation; ATP; phosphorylation; kinase

Figure 1. The electron transport system and the process of oxidative phosphorylation. During oxidative phosphorylation, electrons (e‐) are first transferred in a series of four complexes (the ETS) to generate the mitochondrial membrane potential across the inner mitochondrial membrane (IMM). These electrons are generated by the oxidation of nutrients and the tricarboxylic acid cycle (which occurs in the mitochondrial matrix, not shown). (1) The electron donors NADH and FADH2 feed the ETS via complexes I and II, respectively. (2) Electrons are then transferred to complex III via the electron carrier ubiquinone (Q). (3) Complex III reduces cytochrome c (cyt c) which transfers electrons to the last component of the ETS. (4) Complex IV reduces oxygen (O2) into water (H2O). Simultaneously to the passage of electrons across complexes I, III and IV, protons (H+) are exported across the IMM into the intermembrane space (IMS). (5) This proton motive force is used by the complex V to phosphorylate adenosine diphosphate (ADP) and generate adenosine triphosphate (ATP). The ATP is then exported through the IMM via the adenine nucleotide transporter (ANT) and then across the outer mitochondrial membrane (OMM), via the voltage‐dependent anion channel (VDAC). In the cytosol, endergonic reactions will use ATP and generate ADP, which will be imported within mitochondria to maintain a continuous ATP generation.


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Further Reading

These manuscripts are among the first studies describing the process of oxidative phosphorylation:

Boyer PD (1997) The ATP synthase‐a splendid molecular machine. Annual Review of Biochemistry 66: 717–749.

Chance B and Williams GR (1956) The respiratory chain and oxidative phosphorylation. Advances in Enzymology and Related Subjects of Biochemistry 17: 65–134.

Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi‐osmotic type of mechanism. Nature 191: 144–148.

John E. Walker and Paul D. Boyer received the Nobel prize in 1997 for their works on ATP synthase. These two documents describe their works.

Walker JE (1998) ATP synthesis by rotary catalysis (Nobel Lecture). Annual Review of Biophysics and Biomolecular Structure 28: 205–234.

This manuscript describes the main kinases and phosphatases localized within mitochondria:

Lim S, Smith KR, Lim ST, et al. (2016) Regulation of mitochondrial functions by protein phosphorylation and dephosphorylation. Cell & Bioscience 6: 25.

This article focuses on tyrosine‐phosphorylation events mediated by Src kinases among mitochondrial proteins:

Hebert‐Chatelain E (2013) Src kinases are important regulators of mitochondrial functions. International Journal of Biochemistry and Cell Biology 45: 90–98.

This manuscript describes the role of several types of post‐translational modifications among mitochondrial proteins:

Hofer A and Wenz T (2014) Post‐translational modification of mitochondria as a novel mode of regulation. Experimental Gerontology 56: 202–220.

These manuscripts describe mitochondrial cAMP signalling:

Valsecchi F, Ramos‐Espiritu LS, Buck J, Levin LR and Manfredi G (2013) cAMP and mitochondria. Physiology 28: 199–209.

Zhang F, Zhang L, Qi Y and Xu H (2016) Mitochondrial cAMP signaling. Cellular and Molecular Life Sciences 73: 4577–4590.

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Bou, Marine, Guedouari, Hala, Bujold, Justin, and Hebert‐Chatelain, Etienne(Oct 2017) Role of Protein Phosphorylation among Oxidative Phosphorylation Components. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0027586]