title: Delving deeper: MCL-1's contributions to normal and cancer biology.
abstract: 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.
authors.affiliation: Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Perciavalle
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Opferman
mesh_terms: D017209:Apoptosis / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2