Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: Useful insights from aging and calorie restriction studies

Mitochondrion. 2015 Nov:25:67-75. doi: 10.1016/j.mito.2015.10.001. Epub 2015 Oct 3.


Mitochondrial biogenesis is regulated to adapt mitochondrial population to cell energy demands. Mitochondrial transcription factor A (TFAM) performs several functions for mtDNA and interactions between TFAM and mtDNA participate to regulation of mitochondrial biogenesis. Such interactions are modulated through different mechanisms: regulation of TFAM expression and turnover, modulation of TFAM binding activity to mtDNA through post-translational modifications and differential affinity of TFAM, occurrence of TFAM sliding on mtDNA filaments and of cooperative binding among TFAM molecules, modulation of protein-protein interactions. The tissue-specific regulation of mitochondrial biogenesis in aging and calorie restriction (CR) highlights the relevance of modulation of TFAM-mtDNA interactions.

Keywords: Aging; Calorie restriction; Mitochondrial biogenesis; MtDNA; TFAM; TFAM–mtDNA interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Animals
  • Caloric Restriction*
  • DNA, Mitochondrial / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Mitochondrial Proteins / metabolism*
  • Organelle Biogenesis*
  • Protein Binding
  • Transcription Factors / metabolism*


  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Transcription Factors
  • mitochondrial transcription factor A