During hypoxia, HUMMR joins the mitochondrial dance.
Mitochondrial distribution is integrally related to cellular function. Highly polarized cells, such as neurons, likely depend on mitochondrial transport to maintain proper synaptic function and neurite plasticity. In some cases, mitochondrial transport is also required for cellular migration and proper calcium signaling in non-neuronal cells. Over the past few years, much progress has been made in identifying proteins that control mitochondrial transport and distribution. Miro and Milton, which are two outer mitochondrial membrane proteins, tether mitochondria to kinesin motor proteins. Our recent work identified a novel protein, HUMMR, which interacts with Miro. While present in normoxia, HUMMR protein abundance is markedly induced by hypoxia through a HIF-1 dependent mechanism. Knock down of HUMMR function diminishes the number of mitochondria in the axon, an effect that was more prominent in neurons exposed to hypoxia. Interestingly, in hypoxic neurons, knock down of HUMMR also diminished the number of anterograde moving mitochondria, but increased the number of retrograde moving mitochondria. Thus, HUMMR is a protein which biases mitochondrial movement in the anterograde direction in response to hypoxia. The implication for this biased transport of mitochondria during hypoxia on neuronal function and viability is yet to be discerned. Regardless, since hypoxia is prominent during ischemia and in solid tumors, HUMMR likely contributes to mitochondrial distribution under these conditions. As such, HUMMR may influence cellular function that is dependent upon the correct mitochondrial localization.
Li
Yan
Y
Department of Neurology, Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Rempe
David A
DA
D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological
D024101:Mitochondrial Proteins