Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration

MCL-1 is an anti-apoptotic BCL-2 family member and is frequently upregulated in cancer, but the mechanism by which it promotes cell survival has been elusive. Opferman and colleagues provide insight into this process by showing that MCL-1 exists in different forms with discrete localizations and functions. MCL-1 variants targeted to the outer mitochondrial membrane antagonize BAX and BAK activation, whereas an N-terminally truncated isoform localizes to the mitochondrial matrix and regulates mitochondrial metabolism.