title: Integration of apoptosis and metabolism.
abstract: Apoptotic resistance is a hallmark of human cancers. Recent advances have contributed to our understanding of the molecular mechanisms that intimately integrate cell metabolism and apoptosis. Coordinated activation of the proapoptotic Bcl-2 family and the caspase family during apoptosis often leads to permeabilization of the mitochondrial outer membrane and release of multiple enzymes that normally function in regulating energy production and metabolism. The roles of these metabolic enzymes in promoting caspase activation demonstrate a primordial need to couple apoptotic cell death and metabolic catastrophe during cellular destruction. The Bcl-2 family also directly interacts with the multiple metabolic regulators to protect or promote mitochondrial damage during apoptosis. However, the integration of metabolism and apoptosis is not simply limited to the maintenance of mitochondrial integrity. A recent study demonstrates that the NatA complex, a protein N-α-acetyltransferase complex, is required for DNA damage-mediated apoptosis and suggests that regulation of protein acetylation might provide an important mechanism for regulating apoptotic sensitivity. Since acetyl-CoA (coenzyme A) is a key cofactor for the NatA complex, protein acetylation is subject to the availability of acetyl-CoA and, thus, under metabolic regulation. The revelation that protein N-α-acetylation is regulated by Bcl-xL, a major antiapoptotic mitochondrial protein, demonstrates a mechanism by which metabolism can regulate the activation of multiple key apoptotic factors simultaneously.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Yi
authors.forename: H
authors.initials: H
authors.lastname: Vakifahmetoglu-Norberg
authors.forename: J
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002477:Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
chemical_list: D051017:Apoptosis Regulatory Proteins