How the dominant-negative mutant works. AMPK is an αβγ heterotrimer, and the catalytic α subunit is not functional unless it is complexed with β and γ. Expression in cardiac myocytes of inactive, mutant α2 subunit (red) from a strong promoter (muscle creatine kinase) that gives high expression levels means that expression of the inactive α2 is much higher than that of the endogenous, active α1 and α2 subunits. Because the availability of the β and γ subunits is limiting, most of the heterotrimers formed will contain the inactive, mutant α2. The excess α subunits (not complexed with β and γ) are probably recognized by cellular machinery as misfolded proteins and degraded.