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Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+) uptake and cell death.

ABSTRACT: 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.

SUBMITTER: Piskacek M

PROVIDER: S-EPMC3822876 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Conditional knockdown of hMRS2 results in loss of mitochondrial Mg(2+) uptake and cell death.

Piskacek Martin M Zotova Ludmila L Zsurka Gábor G Schweyen Rudolf J RJ

Journal of cellular and molecular medicine 20080331 4

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 ...[more]

PMID: 18384665

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