HUMMR, a hypoxia- and HIF-1α-inducible protein, alters mitochondrial distribution and transport

Abstract

Mitochondrial transport is critical for maintenance of normal neuronal function. Here, we identify a novel mitochondria protein, hypoxia upregulated mitochondrial movement regulator (HUMMR), which is expressed in neurons and is markedly induced by hypoxiainducible factor 1. (HIF1.). Interestingly, HUMMR interacts with Miro1 and Miro2, mitochondrial proteins that are critical for mediating mitochondrial transport. Interestingly, knockdown of HUMMR or HIF1 function in neurons exposed to hypoxia markedly reduces mitochondrial content in axons. Because mitochondrial transport and distribution are inextricably linked, the impact of reduced HUMMR function on the direction of mitochondrial transport was also explored. Loss of HUMMR function in hypoxia diminished the percentage of motile mitochondria moving in the anterograde direction and enhanced the percentage moving in the retrograde direction. Thus, HUMMR, a novel mitochondrial protein induced by HIF1 and hypoxia, biases mitochondria transport in the anterograde direction. These findings have broad implications for maintenance of neuronal viability and function during physiological and pathological states. © 2009 Li et al.