Figure 1.

Mitochondrial respiratory complex II regulates reserve respiratory capacity and cell survival. Pfleger et al. provides evidence that complex II (Sdh) regulates RRC and cell survival of ventricular cardiomyocytes. Top, schematic representation of electron flow through mitochondrial ETC (CI, II, III and IV refer to mitochondrial ETC complexes I, II, III and IV; IMM, inner mitochondrial membrane; IMS, intermembrane space; NADH, ubiquinone oxidoreductase; OMM, outer mitochondrial membrane). Bottom, detailed structural view of mitochondrial respiration complex II, which is a component of both the TCA cycle and respiratory ETC; it couples substrate utilization to mitochondrial ETC and respiration. Complex II is comprised of four subunits: SDHA, SDHB, SDHC and SDHD, and is the source of RRC, which is critical for cell survival. In this editorial the authors demonstrate that complex II regulates RRC by increasing substrate flux coincident with increased metabolic demand on the cell through TCA and ETC flux. Hypoxia and PDK negatively regulate complex II activity resulting into diminished RRC, ROS and cell death. Activation of AMPK by AICAR or PDH via the inhibition of PDK4 with DCA, rescued RRC, OCR and cell death of cardiomyocytes during hypoxia. Importantly RRC induced by AICAR and DCA is mediated via the class III NAD-dependent deacetylase Sirtuin-3