The first mitochondrial metastasis suppressor: NME4 loss-of-function impairs organelle structure and function

Abstract

NME4 (nucleoside diphosphate kinase D or NM23-H4) is a mitochondrial protein with multiple key functions in bioenergetics and signaling. NME4 mainly localizes to the intermembrane space where it interacts at the inner membrane with cardiolipin and the pro-fusion GTPase OPA1. As part of a metabolite channeling complex, NME4 generates ADP to stimulate respiration and GTP for OPA1 function. NME4 also interacts with outer membrane to favour transfer of cardiolipin to the mitochondrial surface as a pro-mitophagic or -apoptotic signal.