Mitochondrial Translocase of the Outer Membrane Alterations May Underlie Dysfunctional Oxidative Phosphorylation in Alzheimer's Disease

J Alzheimers Dis. 2018;61(2):793-801. doi: 10.3233/JAD-170613.

Abstract

Background: The translocase of the outer membrane (TOM) is a vital mitochondrial transport system facilitating the importation of nuclear encoded proteins into the organelle. While mitochondrial dysfunction, including perturbation of oxidative phosphorylation (OXPHOS) complex, is evident in Alzheimer's disease (AD), it remains unclear whether the observed OXPHOS deficits may be associated with TOM alterations.

Objectives: To correlate TOM subunits with OXPHOS complex proteins in AD.

Methods: Postmortem neocortex (BA40) from AD and age-matched controls were processed to obtain mitochondrial enriched homogenates for the measurement of Tom20, Tom22, Tom40, and Tom70 as well as components of OXPHOS complex I-V by immunoblotting.

Results: Tom20 and Tom70 immunoreactivities were significantly reduced in AD, as were components of OXPHOS complex I and III. Both Tom20 and Tom70 positively correlated with complex III and V, while Tom20 also correlated withcomplex IV.

Conclusion: Reductions in certain TOM subunits and their correlations with specific OXPHOS complex proteins suggest that an impaired mitochondrial transportation system may contribute to previously observed oxidative phosphorylation deficits in AD. Follow-up studies are needed to corroborate the present correlative study.

Keywords: Alzheimer’s disease; mitochondria; oxidative phosphorylation; translocase of the outer membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Autopsy
  • Brain / pathology
  • Female
  • Humans
  • Male
  • Mitochondria / pathology*
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Multivariate Analysis
  • Oxidative Phosphorylation*

Substances

  • Mitochondrial Membrane Transport Proteins