Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan

Autophagy. 2012 Jan;8(1):47-62. doi: 10.4161/auto.8.1.18174. Epub 2012 Jan 1.

Abstract

Mitochondrial health is maintained by the quality control mechanisms of mitochondrial dynamics (fission and fusion) and mitophagy. Decline of these processes is thought to contribute to aging and neurodegenerative diseases. To investigate the role of mitochondrial quality control in aging on the cellular level, human umbilical vein endothelial cells (HUVEC) were subjected to mitochondria-targeted damage by combining staining of mitochondria and irradiation. This treatment induced a short boost of reactive oxygen species, which resulted in transient fragmentation of mitochondria followed by mitophagy, while mitochondrial dynamics were impaired. Furthermore, targeted mitochondrial damage upregulated autophagy factors LC3B, ATG5 and ATG12. Consequently these proteins were overexpressed in HUVEC as an in vitro aging model, which significantly enhanced the replicative life span up to 150% and the number of population doublings up to 200%, whereas overexpression of LAMP-1 did not alter the life span. Overexpression of LC3B, ATG5 and ATG12 resulted in an improved mitochondrial membrane potential, enhanced ATP production and generated anti-apoptotic effects, while ROS levels remained unchanged and the amount of oxidized proteins increased. Taken together, these data relate LC3B, ATG5 and ATG12 to mitochondrial quality control after oxidative damage, and to cellular longevity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Cellular Senescence* / drug effects
  • Chickens
  • Cytoprotection / drug effects
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / pathology*
  • Models, Biological
  • Oxidation-Reduction / drug effects
  • Reactive Oxygen Species / pharmacology
  • Small Ubiquitin-Related Modifier Proteins / metabolism*

Substances

  • ATG12 protein, human
  • ATG5 protein, human
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • Small Ubiquitin-Related Modifier Proteins
  • light chain 3, human
  • Green Fluorescent Proteins