Mitochondrial signaling: the retrograde response

Mol Cell. 2004 Apr 9;14(1):1-15. doi: 10.1016/s1097-2765(04)00179-0.


Mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus that influences many cellular and organismal activities under both normal and pathophysiological conditions. In yeast it is used as a sensor of mitochondrial dysfunction that initiates readjustments of carbohydrate and nitrogen metabolism. In both yeast and animal cells, retrograde signaling is linked to TOR signaling, but the precise connections are unclear. In mammalian cells, mitochondrial dysfunction sets off signaling cascades through altered Ca(2+) dynamics, which activate factors such as NFkappaB, NFAT, and ATF. Retrograde signaling also induces invasive behavior in otherwise nontumorigenic cells implying a role in tumor progression.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Gene Expression Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Mitochondria / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LST8 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae