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Mitochondrial Quality Control as a Therapeutic Target.

Publication ,  Journal Article
Suliman, HB; Piantadosi, CA
Published in: Pharmacol Rev
January 2016

In addition to oxidative phosphorylation (OXPHOS), mitochondria perform other functions such as heme biosynthesis and oxygen sensing and mediate calcium homeostasis, cell growth, and cell death. They participate in cell communication and regulation of inflammation and are important considerations in aging, drug toxicity, and pathogenesis. The cell's capacity to maintain its mitochondria involves intramitochondrial processes, such as heme and protein turnover, and those involving entire organelles, such as fusion, fission, selective mitochondrial macroautophagy (mitophagy), and mitochondrial biogenesis. The integration of these processes exemplifies mitochondrial quality control (QC), which is also important in cellular disorders ranging from primary mitochondrial genetic diseases to those that involve mitochondria secondarily, such as neurodegenerative, cardiovascular, inflammatory, and metabolic syndromes. Consequently, mitochondrial biology represents a potentially useful, but relatively unexploited area of therapeutic innovation. In patients with genetic OXPHOS disorders, the largest group of inborn errors of metabolism, effective therapies, apart from symptomatic and nutritional measures, are largely lacking. Moreover, the genetic and biochemical heterogeneity of these states is remarkably similar to those of certain acquired diseases characterized by metabolic and oxidative stress and displaying wide variability. This biologic variability reflects cell-specific and repair processes that complicate rational pharmacological approaches to both primary and secondary mitochondrial disorders. However, emerging concepts of mitochondrial turnover and dynamics along with new mitochondrial disease models are providing opportunities to develop and evaluate mitochondrial QC-based therapies. The goals of such therapies extend beyond amelioration of energy insufficiency and tissue loss and entail cell repair, cell replacement, and the prevention of fibrosis. This review summarizes current concepts of mitochondria as disease elements and outlines novel strategies to address mitochondrial dysfunction through the stimulation of mitochondrial biogenesis and quality control.

Duke Scholars

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Published In

Pharmacol Rev

DOI

EISSN

1521-0081

Publication Date

January 2016

Volume

68

Issue

1

Start / End Page

20 / 48

Location

United States

Related Subject Headings

  • Thyroid Hormones
  • Polyphenols
  • Pharmacology & Pharmacy
  • Oxidative Phosphorylation
  • Nitric Oxide
  • Mitophagy
  • Mitochondrial Diseases
  • Mitochondria
  • Inflammation Mediators
  • Inflammation
 

Citation

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Suliman, H. B., & Piantadosi, C. A. (2016). Mitochondrial Quality Control as a Therapeutic Target. Pharmacol Rev, 68(1), 20–48. https://doi.org/10.1124/pr.115.011502
Suliman, Hagir B., and Claude A. Piantadosi. “Mitochondrial Quality Control as a Therapeutic Target.Pharmacol Rev 68, no. 1 (January 2016): 20–48. https://doi.org/10.1124/pr.115.011502.
Suliman HB, Piantadosi CA. Mitochondrial Quality Control as a Therapeutic Target. Pharmacol Rev. 2016 Jan;68(1):20–48.
Suliman, Hagir B., and Claude A. Piantadosi. “Mitochondrial Quality Control as a Therapeutic Target.Pharmacol Rev, vol. 68, no. 1, Jan. 2016, pp. 20–48. Pubmed, doi:10.1124/pr.115.011502.
Suliman HB, Piantadosi CA. Mitochondrial Quality Control as a Therapeutic Target. Pharmacol Rev. 2016 Jan;68(1):20–48.
Journal cover image

Published In

Pharmacol Rev

DOI

EISSN

1521-0081

Publication Date

January 2016

Volume

68

Issue

1

Start / End Page

20 / 48

Location

United States

Related Subject Headings

  • Thyroid Hormones
  • Polyphenols
  • Pharmacology & Pharmacy
  • Oxidative Phosphorylation
  • Nitric Oxide
  • Mitophagy
  • Mitochondrial Diseases
  • Mitochondria
  • Inflammation Mediators
  • Inflammation