Kinase signaling cascades in the mitochondrion: A matter of life or death

Craig Horbinski, Charleen T. Chu

Research output: Contribution to journalReview articlepeer-review

208 Scopus citations

Abstract

In addition to powering energy needs of the cell, mitochondria function as pivotal integrators of cell survival/death signals. In recent years, numerous studies indicate that each of the major kinase signaling pathways can be stimulated to target the mitochondrion. These include protein kinase A, protein kinase B/Akt, protein kinase C, extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Although most studies focus on phosphorylation of pro- and antiapoptotic proteins (BAD, Bax, Bcl-2, Bcl-xL), kinase-mediated regulation of complex I activity, anion and cation channels, metabolic enzymes, and Mn-SOD mRNA has also been reported. Recent identification of a number of scaffold proteins (AKAP, PICK, Sab) that bring specific kinases to the cytoplasmic surface of mitochondria further emphasizes the importance of mitochondrial kinase signaling. Immunogold electron microscopy, subcellular fractionation and immunofluorescence studies demonstrate the presence of kinases within subcompartments of the mitochondrion, following diverse stimuli and in neurodegenerative diseases. Given the sensitivity of these signaling pathways to reactive oxygen and nitrogen species, in situ activation of mitochondrial kinases may represent a potent reverse-signaling mechanism for communication of mitochondrial status to the rest of the cell.

Original languageEnglish (US)
Pages (from-to)2-11
Number of pages10
JournalFree Radical Biology and Medicine
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Cancer
  • Free radical
  • Mitochondria
  • Oxidative stress
  • Parkinson's/Lewy body disease
  • Programmed cell death
  • Protein kinases
  • Protein trafficking/translocation
  • Scaffold proteins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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