Mitochondrial Fission in Human Diseases

Handb Exp Pharmacol. 2017:240:159-188. doi: 10.1007/164_2016_38.

Abstract

Mitochondria are an essential component of multicellular life - from primitive organisms, to highly complex entities like mammals. The importance of mitochondria is underlined by their plethora of well-characterized essential functions such as energy production through oxidative phosphorylation (OX-PHOS), calcium and reactive oxygen species (ROS) signaling, and regulation of apoptosis. In addition, novel roles and attributes of mitochondria are coming into focus through the recent years of mitochondrial research. In particular, over the past decade the study of mitochondrial shape and dynamics has achieved special significance, as they are found to impact mitochondrial function. Recent advances indicate that mitochondrial function and dynamics are inter-connected, and maintain the balance between health and disease at a cellular and an organismal level. For example, excessive mitochondrial division (fission) is associated with functional defects, and is implicated in multiple human diseases from neurodegenerative diseases to cancer. In this chapter we examine the recent literature on the mitochondrial dynamics-function relationship, and explore how it impacts on the development and progression of human diseases. We will also highlight the implications of therapeutic manipulation of mitochondrial dynamics in treating various human pathologies.

Keywords: Cancer; DRP1; DRP1S616; Fis1; Fission; Fusion; Mff; Mfn1; Mfn2; MiD49/51; MiD49/51OPA1; Mitochondrial dynamics; Neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dynamins
  • GTP Phosphohydrolases / physiology
  • Humans
  • Mice
  • Microtubule-Associated Proteins / physiology
  • Mitochondria / physiology
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Proteins / physiology
  • Neurodegenerative Diseases / etiology

Substances

  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins