Fusion or Fission: The Destiny of Mitochondria In Traumatic Brain Injury of Different Severities

Sci Rep. 2017 Aug 23;7(1):9189. doi: 10.1038/s41598-017-09587-2.

Abstract

Mitochondrial dynamics are regulated by a complex system of proteins representing the mitochondrial quality control (MQC). MQC balances antagonistic forces of fusion and fission determining mitochondrial and cell fates. In several neurological disorders, dysfunctional mitochondria show significant changes in gene and protein expression of the MQC and contribute to the pathophysiological mechanisms of cell damage. In this study, we evaluated the main gene and protein expression involved in the MQC in rats receiving traumatic brain injury (TBI) of different severities. At 6, 24, 48 and 120 hours after mild TBI (mTBI) or severe TBI (sTBI), gene and protein expressions of fusion and fission were measured in brain tissue homogenates. Compared to intact brain controls, results showed that genes and proteins inducing fusion or fission were upregulated and downregulated, respectively, in mTBI, but downregulated and upregulated, respectively, in sTBI. In particular, OPA1, regulating inner membrane dynamics, cristae remodelling, oxidative phosphorylation, was post-translationally cleaved generating differential amounts of long and short OPA1 in mTBI and sTBI. Corroborated by data referring to citrate synthase, these results confirm the transitory (mTBI) or permanent (sTBI) mitochondrial dysfunction, enhancing MQC importance to maintain cell functions and indicating in OPA1 an attractive potential therapeutic target for TBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries, Traumatic / diagnosis
  • Brain Injuries, Traumatic / etiology
  • Brain Injuries, Traumatic / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics* / genetics
  • Mitophagy / genetics
  • Rats
  • Severity of Illness Index

Substances

  • Biomarkers