A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction

Aging Cell. 2012 Feb;11(1):150-61. doi: 10.1111/j.1474-9726.2011.00769.x. Epub 2011 Dec 28.

Abstract

It is proposed that caloric restriction (CR) increases mitochondrial biogenesis. However, it is not clear why CR increases an energetically costly biosynthetic process. We hypothesized that 40% CR would decrease mitochondrial protein synthesis and would be regulated by translational rather than transcriptional mechanisms. We assessed cumulative mitochondrial protein synthesis over 6 weeks and its transcriptional and translational regulation in the liver, heart, and skeletal muscle of young (6 month), middle (12 month), and old (24 month) male B6D2F1 mice that were lifelong CR or ad lib (AL) controls. Mitochondrial protein synthesis was not different between AL and CR (fractional synthesis over 6 weeks (range): liver, 91-100%; heart, 74-85%; skeletal muscle, 53-72%) despite a decreased cellular proliferation in liver and heart with CR. With CR, there was an increase in AMP-activated protein kinase phosphorylation/total (P:T) in heart and liver, and an increase in peroxisome proliferator-activated receptor gamma coactivator 1-α mRNA in all tissues, but not protein. Ribosomal protein S6 was decreased with CR. In conclusion, CR maintained mitochondrial protein synthesis while decreasing cellular proliferation during a time of energetic stress, which is consistent with the concept that CR increases somatic maintenance. Alternative mechanisms to global translation initiation may be responsible for selective translation of mitochondrial proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Caloric Restriction*
  • Cell Proliferation
  • DNA / biosynthesis
  • Deuterium Exchange Measurement
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Mice
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / metabolism
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / genetics
  • Muscle, Skeletal / metabolism*
  • Myocardium / metabolism*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phosphorylation
  • RNA, Messenger / biosynthesis*

Substances

  • Mitochondrial Proteins
  • PPAR gamma
  • RNA, Messenger
  • DNA
  • AMP-Activated Protein Kinases