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Trypanosome Letm1 protein is essential for mitochondrial potassium homeostasis
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SYSNO ASEP 0420953 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Trypanosome Letm1 protein is essential for mitochondrial potassium homeostasis Tvůrce(i) Hashimi, Hassan (BC-A) RID, ORCID
McDonald, Lindsay M. (BC-A)
Stříbrná, Eva (BC-A)
Lukeš, Julius (BC-A) RID, ORCIDZdroj.dok. Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 288, č. 37 (2013), s. 26914-26925Poč.str. 12 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Bioenergetics ; Letm1 ; Mitochondria ; Potassium Transport ; Translation ; Trypanosome Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP305/12/2261 GA ČR - Grantová agentura ČR Institucionální podpora BC-A - RVO:60077344 UT WOS 000330594500057 DOI 10.1074/jbc.M113.495119 Anotace Letm1 is a conserved protein in eukaryotes bearing energized mitochondria. Hemizygous deletion of its gene has been implicated in symptoms of the human disease Wolf-Hirschhorn syndrome. Studies almost exclusively performed in opisthokonts have attributed several roles to Letm1, including maintaining mitochondrial morphology, mediating either calcium or potassium/proton antiport, and facilitating mitochondrial translation. We address the ancestral function of Letm1 in the highly diverged protist and significant pathogen, Trypanosoma brucei. We demonstrate that Letm1 is involved in maintaining mitochondrial volume via potassium/proton exchange across the inner membrane. This role is essential in the vector-dwelling procyclic and mammal-infecting bloodstream stages as well as in Trypanosoma brucei evansi, a form of the latter stage lacking an organellar genome. In the pathogenic bloodstream stage, the mitochondrion consumes ATP to maintain an energized state, whereas that of T. brucei evansi also lacks a conventional proton-driven membrane potential. Thus, Letm1 performs its function in different physiological states, suggesting that ion homeostasis is among the few characterized essential pathways of the mitochondrion at this T. brucei life stage. Interestingly, Letm1 depletion in the procyclic stage can be complemented by exogenous expression of its human counterpart, highlighting the conservation of protein function between highly divergent species. Furthermore, although mitochondrial translation is affected upon Letm1 ablation, it is an indirect consequence of K(+) accumulation in the matrix. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2015
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