M-LDH as a regulatory subunit in the cytosolic substrate channelling complex. (360G-Wellcome-082577_Z_07_Z)

Nucleoside diphosphate kinase A (NDPK-A) selectively regulates the alpha1 isoform of the AMP-activated protein kinase (AMPK alpha1), independently of [AMP] and surrounding [ATP], by a process termed substrate channelling . Our preliminary data shows that the muscle form (M-LDH or LDH-A) but not the heart form (H-LDH or LDH-B), of lactate dehydrogenase is physically associated with the rat liver cytosolic substrate channelling complex and NDPK-B, such that M-LDH associates with NDPK-A, AMPK alp ha1 and CK2 and H-LDH associates with NDPK-B. Further, we have evidence that the species of LDH bound to the substrate channelling complex regulates the in vitro enzymatic activity of both AMPK and CK2. Thus, we hypothesise that M-LDH forms an integral part of the cytosolic substrate channelling complex in vivo where it is capable of regulating the substrate channelling mechanism, allowing for efficient sensing of cellular metabolic status and redox potential. Our research aims to further inv estigate these novel findings, characterise the molecular interactions of LDH in the complex and understand the functional relevance of LDH as a regulatory subunit of the substrate channelling complex.