Emerging roles of lipids in BCL-2 family-regulated apoptosis

Apoptosis is an intricately regulated process required for the health and homeostasis of living systems. The mitochondrial apoptotic pathway depends on the BCL-2 family of pro- and anti-apoptotic members whose interactions form a complex network of checks and balances in regulating cell fate. A diverse set of signals recruits distinct BH3-domain only BCL-2 proteins to trigger activation of the executioner proteins BAX and BAK. In addition to protein components of the apoptotic machinery, literature of the past several decades supports crucial functions for lipids in apoptosis and cooperation between lipid metabolism and BCL-2 proteins. In this review we present the two key examples of ceramide and cardiolipin in apoptosis, focusing particularly on BCL-2 family-regulated pathways at the mitochondrial level. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.