Korean Circ J.  2016 Jan;46(1):1-12. 10.4070/kcj.2016.46.1.1.

Post-Translational Modifications of Cardiac Mitochondrial Proteins in Cardiovascular Disease: Not Lost in Translation

• Marquez J
• Lee SR
• Kim N
• Han J

• KMID: 2223763
• DOI: http://doi.org/10.4070/kcj.2016.46.1.1

Abstract

Protein post-translational modifications (PTMs) are crucial in regulating cellular biology by playing key roles in processes such as the rapid on and off switching of signaling network and the regulation of enzymatic activities without affecting gene expressions. PTMs lead to conformational changes in the tertiary structure of protein and resultant regulation of protein function such as activation, inhibition, or signaling roles. PTMs such as phosphorylation, acetylation, and S-nitrosylation of specific sites in proteins have key roles in regulation of mitochondrial functions, thereby contributing to the progression to heart failure. Despite the extensive study of PTMs in mitochondrial proteins much remains unclear. Further research is yet to be undertaken to elucidate how changes in the proteins may lead to cardiovascular and metabolic disease progression in particular. We aimed to summarize the various types of PTMs that occur in mitochondrial proteins, which might be associated with heart failure. This study will increase the understanding of cardiovascular diseases through PTM.

Keyword

Cardiovascular diseases; Heart failure; Mitochondria; Post-translational modifications

MeSH Terms

Acetylation
Cardiovascular Diseases*
Gene Expression
Heart Failure
Metabolic Diseases
Mitochondria
Mitochondrial Proteins*
Phosphorylation
Protein Processing, Post-Translational*
Mitochondrial Proteins

Figure

• 

  Fig. 1 Several types of post-translational modifications. (A) Reversible protein phosphorylation. Protein kinase transfers a phosphate group (P) from ATP (ADPP) to the target protein. A protein phosphatase is responsible for removing the phosphate group via hydrolysis. (B) Protein kinases mediate phosphorylation at various amino acid sites of serine, threonine and tyrosine side chains. In the example shown, PDH is a phosphorylated protein found in the mitochondrial matrix. PDH is a large complex made up of several units (E1, E2, and E3), which is responsible for catalyzing oxidative decarboxylation of pyruvate, to form acetyl-CoA. PDH is phosphprylated at Ser264, 271, and 204. (C) Reversible protein acetylation. In the given example, Sirtuin 3 (SIRT3) deacetylases the acetylated form of NDUFA9. (D) Redox-mediated S-nitrosylation occurs through the covalent reaction of nitric oxide (NO)-related species with a cysteine thiol group on the target protein. ATP: adenosine triphosphate, ADP: adenosine diphosphate, PDH: pyruvate dehydrogenase, Ser: serine, NDUFA9: NADH dehydrogenase subcomplex A9, NO: nitric oxide, CI: complex I, SH: thiol subunit, S: sulfur.

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