LETM1 exchanges protons (mitochondrial intermembrane space) for calcium (mitochondrial matrix)

Stable Identifier
Reaction [transition]
Homo sapiens
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LETM1, which is located in the mitochondrial inner membrane (Tamai et al. 2008), exchanges two protons from the mitochondrial intermembrane space for a divalent calcium ion from the mitochondrial matrix (Tsai et al. 2014, Shao et al. 2016). LETM1 appears to participate in both calcium efflux and calcium influx (Doonan et al. 2014). Overexpression of LETM1, however, does not elevate calcium efflux from the mitochondrial matrix so the role of LETM1 in mitochondrial calcium flux is controversial (De Marchi et al. 2014). In human HeLa cells, knockdown of LETM1 causes an increase in mitochondrial calcium (Shao et al. 2016) however in mice, knockdown of Letm1 causes a reduction in mitochondrial calcium uptake and proton extrusion at low cytosolic calcium concentration (Jiang et al. 2013). LETM1 has also been proposed to act as a K+/H+ exchanger (Froschauer et al. 2005).
Literature References
PubMed ID Title Journal Year
24898248 NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby limiting Ca2+-induced NAD(P)H production and modulating matrix redox state

De Marchi, U, Castelbou, C, Sekler, I, Santo-Domingo, J, Wiederkehr, A, Demaurex, N

J. Biol. Chem. 2014
23716663 Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome

Clapham, DE, Zhao, L, Clish, CB, Jiang, D

Proc. Natl. Acad. Sci. U.S.A. 2013
18628306 Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L

Iida, H, Sayano, T, Hayashi, J, Yokota, S, Tamai, S, Kiguchiya, S, Oka, T, Ishihara, N, Mihara, K

J. Cell. Sci. 2008
19797662 Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter

Clapham, DE, Zhao, L, Jiang, D

Science 2009
24344246 Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1

Clapham, D, Miller, C, Zhao, L, Tsai, MF, Jiang, D

J. Gen. Physiol. 2014
25077561 LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation

Cárdenas, C, Hoffman, NE, Shanmughapriya, S, Madesh, M, Foskett, JK, Chen, X, Doonan, PJ, Cheung, JY, Chandramoorthy, HC, Vallem, S, Houser, SR, Rajan, S, Zhang, X

FASEB J. 2014
27669901 Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca(2+)/H(+) antiporter

Ji, Y, Shao, J, Yang, X, Fu, Z, Ding, Z, Guan, X, Shen, Y, Cong, Y, Guo, S

Sci Rep 2016
15904662 Electroneutral K+/H+ exchange in mitochondrial membrane vesicles involves Yol027/Letm1 proteins

Nowikovsky, K, Schweyen, RJ, Froschauer, E

Biochim. Biophys. Acta 2005
Catalyst Activity

calcium:proton antiporter activity of LETM1 hexamer [mitochondrial inner membrane]

Inferred From
Cross References
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