Lipophorin receptor 1 (LpR1) in Drosophila muscle influences life span by regulating mitochondrial aging

Biochem Biophys Res Commun. 2021 Sep 3:568:95-102. doi: 10.1016/j.bbrc.2021.06.080. Epub 2021 Jun 30.

Abstract

Sarcopenia is a syndrome characterized by progressive loss of muscle mass and function during aging. Although mitochondrial dysfunction and related metabolic defects precede age-related changes in muscle, their contributions to muscle aging are still not well known. In this study, we used a Drosophila model to investigate the role of lipophorin receptors (LpRs), a Drosophila homologue of the mammalian very low-density lipoprotein receptor (VLDLR), in mitochondrial dynamics and muscle aging. Muscle-specific knockdown of LpR1 or LpR2 resulted in mitochondrial dysfunction and reduced proteostasis, which contributed to muscle aging. Activation of AMP-activated protein kinase (AMPK) ameliorated muscle dysfunction induced by LpR1 knockdown. These results suggest that LpR1/VLDLR is a novel key target that modulates age-dependent lipid remodeling and muscle homeostasis.

Keywords: Aging; Drosophila model; Lipoprotein receptor; Mitochondria; Sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Gene Knockdown Techniques
  • Longevity
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Turnover
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Drosophila Proteins
  • Lpr1 protein, Drosophila
  • Receptors, Cytoplasmic and Nuclear