MtDNA germ line variation mediated ROS generates retrograde signaling and induces pro-cancerous metabolic features.

ABSTRACT: mtDNA non-synonymous germ line variation (G10398A; p.A114T) has remained equivocal with least mechanistic understanding in showing an association with cancer. This has necessitated showing in-vitro how an over-expression within mitochondria of either of the variants produces higher intracellular ROS, resulting in differential anchorage dependent and independent growth. Both these features were observed to be relatively higher in ND3:114T variant. An elevated amount of intracellular carbonylated proteins and a reduced activity of a key glycolytic enzyme, Pyruvate kinase M2, along with high glucose uptake and lactate production were other pro-cancerous features observed. The retrograde signaling through surplus ROS was generated by post-ND3 over-expression regulated nuclear gene expression e

SUBMITTER: Singh RK 

PROVIDER: S-EPMC4192639 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature