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

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

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Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA.


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.

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