Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+) uptake and cell death.
The human gene MRS2L encodes a mitochondrial protein distantly related to CorA Mg(2+) transport proteins. Constitutive shRNA-mediated knockdown of hMRS2 in human HEK-293 cell line was found here to cause death. To further study its role in Mg(2+) transport, we have established stable cell lines with conditionally expressing shRNAs directed against hMRS2L. The cells expressing shRNA for several generations exhibited lower steady-state levels of free mitochondrial Mg(2+) ([Mg(2+)](m)) and reduced capacity of mitochondrial Mg(2+) uptake than control cells. Long-term expression of shRNAs resulted in loss of mitochondrial respiratory complex I, decreased mitochondrial membrane potential and cell death. We conclude that hMrs2 is the major transport protein for Mg (+) uptake into mitochondria and that expression of hMrs2 is essential for the maintenance of respiratory complex I and cell viability.
Piskacek
Martin
M
Department of Genetics, Vienna University, Austria.
Zotova
Ludmila
L
Zsurka
Gábor
G
Schweyen
Rudolf J
RJ
D027682:Cation Transport Proteins / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
D027682:Cation Transport Proteins; C430096:MRS2 protein, human; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D008274:Magnesium