Mitophagy Decreases in the Peripheral Vestibular System of Aged C57BL/6J Mice

In Vivo. 2024 Jan-Feb;38(1):196-204. doi: 10.21873/invivo.13426.

Abstract

Background/aim: Mitophagy is a cardinal process for maintaining healthy and functional mitochondria. A decline in mitophagy has been associated with age-related pathologies. We aimed to investigate mitophagy changes in age-related balance problems using an animal model.

Materials and methods: C57BL/6J mice were divided into young (1 month old) and aged (12 months old) groups. Balance performance, mitochondrial DNA integrity, ATP content, mitophagic process, and mitophagy-related genes and proteins were investigated in both groups.

Results: Balance and motor performance were reduced in the aged group. Mitochondrial DNA integrity and ATP content, and mRNA levels of PINK1, Parkin, BNIP3, AMBRA1, MUL1, NIX, Bcl2-L-13, Atg3, Atg5, Atg12, and Atg13 in the vestibule were significantly lower in aged mice compared with those in young mice. The protein levels of PINK1, Parkin, BNIP3, LC3B, and OXPHOS subunits were significantly decreased in the aged vestibule. Mitophagosome and mitophagolysosome counts and the immunohistochemical expression of Parkin and BNIP3 were also decreased in the saccule, utricle, and crista ampullaris in the aged group.

Conclusion: A general decrease in mitophagy with aging might be attributed to a decrease in cellular function in the aged vestibule during the development of age-related balance problems.

Keywords: Mitophagy; aging; mice; vestibular system.

MeSH terms

  • Adenosine Triphosphate*
  • Animals
  • DNA, Mitochondrial
  • Mice
  • Mice, Inbred C57BL
  • Mitophagy* / genetics
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Vestibular System

Substances

  • Adenosine Triphosphate
  • Ubiquitin-Protein Ligases
  • Protein Kinases
  • DNA, Mitochondrial