Delving deeper: MCL-1's contributions to normal and cancer biology

Trends Cell Biol. 2013 Jan;23(1):22-9. doi: 10.1016/j.tcb.2012.08.011. Epub 2012 Sep 28.


BCL-2 molecules are regulators of programmed cell death and defects in this pathway contribute to human diseases. One family member, MCL-1, is unique because its expression is tightly regulated and it is essential for promoting the survival of myriad cellular lineages. Additionally, MCL-1 promotes the maintenance of normal mitochondrial morphology and energy production. Dissection of these functions revealed recently that they depend on separate mitochondrial sublocalizations. MCL-1's antiapoptotic activity is restricted to the outer mitochondrial membrane (OMM), whereas its function in mitochondrial physiology requires localization to the matrix. These findings provide an attractive model for how MCL-1's diverse functions may contribute to normal cell homeostasis and function. MCL-1 is highly amplified in human cancer, suggesting that these functions may contribute to malignant cell growth and evasion of apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / genetics
  • Cell Lineage / genetics
  • Cell Transformation, Neoplastic*
  • Gene Expression Regulation, Neoplastic
  • Homeostasis / genetics
  • Humans
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism


  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2