All the little pieces

Regulation of mitochondrial fusion and fission by ubiquitin and small ubiquitin-like modifier and their potential relevance in the heart

Zungu Makhosazane, Schisler Jonathan, Monte Willis

Research output: Contribution to journalReview article

46 Citations (Scopus)

Abstract

Mitochondria are dynamic organelles that undergo a constant cycle of division and fusion to maintain their function. The process of mitochondrial fusion has the effect of mixing their content, allowing complementation of protein components, mtDNA repair, and distribution of metabolic intermediates. Fission, on the other hand, enables mitochondria to increase in number and capacity, and to segregate mitochondria for autophagy by the lysosome ("mitophagy"). Disruption of these protein quality control mechanisms has recently been identified in multiple cardiac diseases, including cardiac hypertrophy, heart failure, dilated cardiomyopathy, and ischemic heart disease, and is intimately tied to mitochondrial control of apoptosis. Proteins that regulate mitochondrial fusion and fission have been discovered, including Mfn1, Mfn2, and Opa1 (fusion) and Drp1 and Fis1 (fission). In this review, we discuss how these proteins are regulated by post-translational modification with ubiquitin and SUMO (small ubiquitin-like modifier). We then present what is known about the ubiquitin and SUMO ligases that regulate these post-translational modifications and regulation of mitochondrial fusion and fission, exploring their potential as therapeutic targets of cardiac disease.

Original languageEnglish (US)
Pages (from-to)2513-2521
Number of pages9
JournalCirculation Journal
Volume75
Issue number11
DOIs
StatePublished - Oct 31 2011
Externally publishedYes

Fingerprint

Mitochondrial Dynamics
Ubiquitin
Mitochondria
Post Translational Protein Processing
Heart Diseases
Mitochondrial Degradation
Proteins
Autophagy
Dilated Cardiomyopathy
Cardiomegaly
Ligases
Lysosomes
Mitochondrial DNA
Quality Control
Organelles
Myocardial Ischemia
Heart Failure
Apoptosis

Keywords

  • Heart
  • Mitochondrial dynamics
  • SUMO
  • Ubiquitin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

All the little pieces : Regulation of mitochondrial fusion and fission by ubiquitin and small ubiquitin-like modifier and their potential relevance in the heart. / Makhosazane, Zungu; Jonathan, Schisler; Willis, Monte.

In: Circulation Journal, Vol. 75, No. 11, 31.10.2011, p. 2513-2521.

Research output: Contribution to journalReview article

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