Carla M. Koehler, Ph.D.

Laboratory Address:
Young Hall 4043

Mailing Address:
Mail Code: 156905
607 Charles Young Drive East
Los Angeles, CA 90095

Work Address:
Young Hall 4041A

Lab Director, Koehler Lab
Professor, Chemistry and Biochemistry, Biochemistry, Molecular Biology
Member, Brain Research Institute, Cell & Developmental Biology GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, themes
Researcher, Biochemistry, Chemical Biology
Research Interests
A basic question of cell biology is the mechanism by which a protein reaches its correct location within the cell. Of all the organelles in a mammalian cell, the mitochondrion is the most complex because two membranes must be crossed. In addition to the metabolic role, the mitochondria is a key player in many cellular processes including apoptosis, metal ion homeostasis and aging. My specific interests lie in mitochondrial biogenesis, particularly the mechanism by which proteins are imported into the mitochondrial inner membrane. Our laboratory uses a combined genetic and biochemical approach to understand this basic process in the model organism Saccharomyces cerevisae. But we have expanded into mammalian systems now with the identification of the molecular basis of a mitochondrial disease with symptoms of deafness, blindness, and movement disorders. This disease is caused by a defect in import of inner membrane proteins. Current studies continue in both mammalian and yeast systems. Our broad interests are to understand mitochondrial biogenesis and how it relates to cellular homeostasis.

Professor Koehler has been a faculty member in the Department of Chemistry and Biochemistry since 1999. She came to UCLA after doing post-doctoral research in the laboratory of Dr Gottfried Schatz at the Biozentrum, Basel, Switzerland. Her research characterized a new protein import pathway in the mitochondrion and linked a defect in protein import with the inherited disease deafness-dystonia syndrome. Dr. Koehler completed her graduate studies at Iowa State University, characterizing the inheritance of mitochondrial DNA during her M.S. studies and studying dimorphism in Saccharomyces cerevisiae. Dr. Koehler is a former Damon Runyon Scholar and current Established Investigator of the American Heart Association. Dr. Koehler is an Associate Editor for Current Genetics. She has been a member of the Molecular Biology Institute, Jonsson Cancer Center, and the Brain Research Institute since 1999. Her current research focuses on developing vertebrate models for mitochondrial diseases as well as using yeast for mechanistic studies on mitochondrial biogenesis.

Dabir Deepa V, Hasson Samuel A, Setoguchi Kiyoko, Johnson Meghan E, Wongkongkathep Piriya, Douglas Colin J, Zimmerman Johannes, Damoiseaux Robert, Teitell Michael A, Koehler Carla M A small molecule inhibitor of redox-regulated protein translocation into mitochondria. Developmental cell. 2013; 25(1): 81-92.
Arango Nelson Alexander, Li Li, Dabir Deepa, Nicolau Fotini, Pieretti-Vanmarcke Rafael, Koehler Carla, McCarrey John R, Lu Naifang, Donahoe Patricia K Meiosis I arrest abnormalities lead to severe oligozoospermia in meiosis 1 arresting protein (M1ap)-deficient mice. Biology of reproduction. 2013; 88(3): 76.
Zhang Jin, Nuebel Esther, Daley George Q, Koehler Carla M, Teitell Michael A Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. Cell stem cell. 2012; 11(5): 589-95.
Bourens Myriam, Dabir Deepa V, Tienson Heather L, Sorokina Irina, Koehler Carla M, Barrientos Antoni Role of twin Cys-Xaa9-Cys motif cysteines in mitochondrial import of the cytochrome C oxidase biogenesis factor Cmc1. The Journal of biological chemistry. 2012; 287(37): 31258-69.
Claypool Steven M, Koehler Carla M The complexity of cardiolipin in health and disease. Trends in biochemical sciences. 2012; 37(1): 32-41.
Claypool Steven M, Whited Kevin, Srijumnong Santi, Han Xianlin, Koehler Carla M Barth syndrome mutations that cause tafazzin complex lability. The Journal of cell biology. 2011; 192(3): 447-62.
Curado Silvia, Ober Elke A, Walsh Susan, Cortes-Hernandez Paulina, Verkade Heather, Koehler Carla M, Stainier Didier Y R The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model. Disease models & mechanisms. 2010; 3(7-8): 486-95.
Zaltsman Yehudit, Shachnai Liat, Yivgi-Ohana Natalie, Schwarz Michal, Maryanovich Maria, Houtkooper Riekelt H, Vaz Frédéric Maxime, De Leonardis Francesco, Fiermonte Giuseppe, Palmieri Ferdinando, Gillissen Bernhard, Daniel Peter T, Jimenez Erin, Walsh Susan, Koehler Carla M, Roy Soumya Sinha, Walter Ludivine, Hajnóczky György, Gross Atan MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria. Nature cell biology. 2010; 12(6): 553-62.
Hasson Samuel A, Damoiseaux Robert, Glavin Jenny D, Dabir Deepa V, Walker Scott S, Koehler Carla M Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(21): 9578-83.
Tienson Heather L, Dabir Deepa V, Neal Sonya E, Loo Rachel, Hasson Samuel A, Boontheung Pinmanee, Kim Sung-Kun, Loo Joseph A, Koehler Carla M Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins. Molecular biology of the cell. 2009; 20(15): 3481-90.
Lu, G., H. Sun, P. Korge, C. M. Koehler, J. N. Weiss, and Y. Wang Functional characterization of a mitochondrial Ser/Thr protein phosphatase in cell death regulation. Methods Enzymol. 2009; 457: 255-273.
Chacinska A., C. M. Koehler, D. Milenkovic, T. Lithgow, and N. Pfanner Importing mitochondrial proteins: machineries and mechanisms. Cell. 2009; 138: 628-644.
Tienson, H. L., D. V. Dabir, S. E. Neal, R. Loo, S. A. Hasson, P. Boontheung, S.-K. Kim, J. A. Loo, and C. M. Koehler Reconstitution of the Mia40-Erv1 oxidative folding pathway for the small Tim proteins. Mol. Biol. Cell. 2009; 20: 3481-3490.
Koehler, C. M. and H. L. Tienson Redox regulation of protein folding in the mitochondrial intermembrane space. Biochim Biophys Acta. 2009; 1793: 139-145.
Koehler Carla M, Tienson Heather L Redox regulation of protein folding in the mitochondrial intermembrane space. Biochimica et biophysica acta. 2009; 1793(1): 139-45.
Claypool Steven M, Boontheung Pinmanee, McCaffery J Michael, Loo Joseph A, Koehler Carla M The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. Molecular biology of the cell. 2008; 19(12): 5143-55.
Beverly Kristen N, Sawaya Michael R, Schmid Einhard, Koehler Carla M The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23. Journal of molecular biology. 2008; 382(5): 1144-56.
Claypool Steven M, Oktay Yavuz, Boontheung Pinmanee, Loo Joseph A, Koehler Carla M Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. The Journal of cell biology. 2008; 182(5): 937-50.
Walsh Susan, Koehler Carla M Gazing at translocation in the mitochondrion. Cell. 2008; 134(3): 382-3.
Gebert, N., A. Chacinska, K. Wagner, B. Guiard, C. M. Koehler, P. Rehling, N. Pfanner, and N. Wiedemann Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. EMBO Rep. 2008; 9: 548-554.
Claypool, S. M., Y. Oktay, P. Boontheung, J. A. Loo, and C. M. Koehler Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. J. Cell Biol. 2008; 182: 937-950.
Walsh, S. and C. M. Koehler Gazing at translocation in the mitochondrion. Cell. 2008; 134: 382-383.
Beverly, K. N., M, R. Sawaya, E. Schmid, and C. M. Koehler The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23. J. Mol. Biol. 2008; 382: 1144-1156.
Claypool, S. M., P. Boontheung, J. M. McCaffery, J. A. Loo, and C. M. Koehler The cardiolipin transacylase, Tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. Mol. Biol. Cell. 2008; 19: 5143-5155.
Dabir Deepa V, Leverich Edward P, Kim Sung-Kun, Tsai Frederick D, Hirasawa Masakazu, Knaff David B, Koehler Carla M A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1. The EMBO journal. 2007; 26(23): 4801-11.
Hwang David K, Claypool Steven M, Leuenberger Danielle, Tienson Heather L, Koehler Carla M Tim54p connects inner membrane assembly and proteolytic pathways in the mitochondrion. The Journal of cell biology. 2007; 178(7): 1161-75.
Lu G., Ren S., Korge P., Choi J., Dong Y., Weiss J., Koehler C., Chen J.N., Wang Y. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes Dev. 2007; 21: 784-796.
Dabir, D. V., E. P. Leverich, S.-K. Kim, F. D. Tsai, M. Hirasawa, D. B. Knaff, and C. M. Koehler A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1. EMBO J 2007; 26: 4801-4811.
Sediva, A., C. I. E. Smith, A. C. Asplund, J. Hadac, A. Janda, J. Zeman, H. Hansikova; L. Dvorakova, L. Mrazova, S. Velbri, C. Koehler, K. Roesch, K. E. Sullivan, T. Futatani, H. Ochs Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L and DRP2 genes. J. Clin. Immunol. 2007; 27: 640-646.
Chen, H.-W., C. M. Koehler, and M. A. Teitell Human polynucleotide phosphorylase: Location matters. Trends Cell Biol 2007; 17: 600-608.
Stuart, R.A. and C.M. Koehler In Vitro Analysis of Yeast Mitochondrial Protein Import. In Morgan, K. (ed.) Current Protocols in Cell Biology 2007; 11.19.1-11.19.20.
French S.W., Dawson D.W., Chen H.W., Rainey R.N., Sievers S.A., Balatoni C.E., Wong L., Troke J.J., Nguyen M.T., Koehler C.M., Teitell M.A. The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity. Cancer Letts. 2007; 248: 198-210.
Oktay, Y., R.N.Rainey, and C.M. Koehler The function of TIM22 in the insertion of inner membrane proteins in mitochondria. Dalbey, R.E., Koehler, C.M., and Tamanoi, F. (eds.) The Enzymes: Molecular Machines Involved in Protein Transport across Membrane 2007; 25: 367-386.
Hwang, D. K., S. M. Claypool, H. D. Tienson, D. Leuenberger, C. M. Koehler Tim54p mediates assembly of the <i>i</i>-AAA protease Yme1p. J. Cell Biol. 2007; 178: 1161-75.
Claypool Steven M, McCaffery J Michael, Koehler Carla M Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins. The Journal of cell biology. 2006; 174(3): 379-90.
Rainey R.N., Glavin J.D., Chen H.W., French S.W., Teitell M.A., Koehler C.M. A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space. Mol. Cell. Biol. 2006; 26(22): 8488-8497.
Chen, H.W., Rainey, R.N., Balatoni C.E., Dawson D.W., Troke J.J., Wasiak S., Hong J.S., McBride H.M., Koehler C.M., Teitell M.A., French S.W. Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis. Mol. Cell. Biol. 2006; 26(22): 8475-8487.
Claypool, S.M., McCaffery, J.M., Koehler, C.M. Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins. J. Cell Biol 2006; 184: 379-390.
Koehler, C.M., Beverly, K.N., Leverich, E.P. Redox Pathways of the Mitochondrion. Antioxid. Redox. Signal 2006; 8: 813-822.
Claypool SM, Koehler CM Hereditary spastic paraplegia: respiratory choke or unactivated substrate?. Cell. . 2005; 123(2): 183-5.
Claypool Steven M, Koehler Carla M Hereditary spastic paraplegia: respiratory choke or unactivated substrate?. Cell. 2005; 123(2): 183-5.
Likic VA, Perry A, Hulett J,Derby M, Traven A, Waller RF, Keeling PJ, Koehler CM, Curran SP, Gooley PR and Lithgow T Patterns that define the four domains conserved in known and novel isoforms of the protein import receptor Tom20. J. Mol. Biol. 2005; 347: 81-93.
Koehler CM, Hwang DK Protein translocation across membranes. Encyclopedia of Molecular Cell Biology and Molecular Medicine 2005; 11: 287-308.
Curran SP, Leverich EP, Koehler CM, Larsen PL Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development. The Journal of biological chemistry. . 2004; 279(52): 54655-62.
Curran SP, Leuenberger D, Leverich EP, Hwang DK, Beverly KN, Koehler CM The role of Hot13p and redox chemistry in the mitochondrial TIM22 import pathway. The Journal of biological chemistry. . 2004; 279(42): 43744-51.
Curran SP and Koehler CM Mitochondrial biogenesis. Protein import into and across the inner membrane. Topics in Current Genetics: Mitochondrial Function and Biogenesis 2004; 8: 59-80.
Koehler CM New developments in mitochondrial assembly. Annual review of cell and developmental biology. . 2004; 20: 309-35.
Leuenberger D, Curran SP and Koehler CM Structure, bioenergetics, and biogenesis of mitochondria. The Biogenesis of Cellular Organelles 2004; 138-163.
Roesch K, Hynds PH, Varga R, Tranebjaerg L and Koehler CM The calcium-binding apartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex. Hum. Mol. Gen. 2004; 13: 2101-2111.
Koehler CM The small Tim proteins and the twin Cx3C motif. Trends in biochemical sciences. . 2004; 29(1): 1-4.
Koehler CM Import and assembly. Genetics of Mitochondrial Diseases 2003; 47-68.
Dyall SD, Lester DC, Schneider RE, Delgadillo-Correa MG, Plumper E, Martinez A, Koehler CM, Johnson PJ Trichomonas vaginalis Hmp35, a putative pore-forming hydrogenosomal membrane protein, can form a complex in yeast mitochondria. J. Biol. Chem. 2003; 278: 30548-30461.
van der Bliek AM, Koehler CM A mitochondrial rhomboid protease. Developmental cell. . 2003; 4(6): 769-70.
Leuenberger D, Curran SP, Wong D, Koehler CM The role of Tim9p in the assembly of the TIM22 import complexes. Traffic (Copenhagen, Denmark) . 2003; 4(3): 144-52.
Curran SP, Leuenberger D, Schmidt E, Koehler CM The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins. The Journal of cell biology. . 2002; 158(6): 1017-27.
Roesch K, Tranejaerg L, Koehler CM How do defects in mitochondrial protein import lead to deafness. 19th Danavox Symposium: Genetics and the function of the auditory system. 2002; 19: 139-154.
Roesch K, Curran SP, Tranebjaerg L and Koehler CM Human deafness dystonia syndrome is caused by a defect in asssembly of the DDP1/TIMM8a-TIMM13 complex. Hum. Mol. Gent. 2002; 11: 477-486.
Curran SP, Leuenberger D, Oppliger W, Koehler CM The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier. The EMBO journal. . 2002; 21(5): 942-53.
Murphy MP, Leuenberger D, Curran SP, Oppliger W and Koehler CM The essential function of the small tim proteins in the tim22 import pathway does not depend on formation of the soluble 70-kilodalton complex. Mol. Cell. Biol. 2001; 21: 6132-6138.
Renold A, Koehler CM and Murphy MP Mitochondrial import of the long and short isoforms of human uncoupling protein 3. FEBS Lett. 2000; 465: 135-140.
Koehler CM Protein translocation pathways of the mitochondrion. FEBS Lett. 2000; 476(1-2): 27-31.
Dyall SM, Koehler CM, Delgadillo MG, Bradley PJ, Plumper E, Leuenberger D, Turck CW and Johnson PJ The presence of mitochondria carrier in the hydrogenosomal membranes: conservation of membrane targeting pathways indicated a progenitor organelle gave rise to hydrogenosomes and mitochondria. Mol. Cell. Biol. 2000; 20: 2488-2497.
Koehler CM, Murphy MP, Bally NA, Oppliger W, Dolfini L, Junne T and Or E Tim18p, a novel subunit of the inner membrane complex that mediates protein import into the yeast mitochondrial inner membrane. Mol. Cell. Biol. 2000; 20: 1187-1193.
Patterson SD, Spahr CS, Daugas E, Susin SA, Irinopoulou T, Koehler C, Kroemer G Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition. Cell death and differentiation. . 2000; 7(2): 137-44.
Koehler CM, Merchant S, Schatz G How membrane proteins travel across the mitochondrial intermembrane space. Trends in biochemical sciences. . 1999; 24(11): 428-32.
Leuenberger D, Bally NA, Schatz G, Koehler CM Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. The EMBO journal. . 1999; 18(17): 4816-22.
Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T and Schatz G Human deafness dystonia syndrome is a mitochondrial disease. Proc. Natl. Acad. Sci. (USA). 1999; 96: 2141-2146.
Komiya T, Rospert S, Koehler CM, Looser R, Schatz G, and Mihara K Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: Evidence for the "acid chain" hypothesis. EMBO J 1998; 17: 3886-3898.
Koehler CM, Merchant S, Oppliger W, Schmid K, Jarosch E, Dolfini L, Junne T, Schatz G and Tokatlidis K Tim9p, an essential partner of Tim10p for the import of mitochondrial carriers. EMBO J. 1998; 17: 6477-6486.
Koehler CM, Jarosch E, Tokatlidis K, Schmid K, Schweyen RJ, Schatz G Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science. . 1998; 279(5349): 369-73.
Koehler CM, Myers AM Serine-threonine protein kinase activity of Elm1p, a regulator of morphologic differentiation in Saccharomyces cerevisiae. FEBS letters. . 1997; 408(1): 109-14.
Blacketer MJ, Koehler CM, Coats SG, Myers AM, Madaule P Regulation of dimorphism in Saccharomyces cerevisiae: involvement of the novel protein kinase homolog Elm1p and protein phosphatase 2A. Molecular and cellular biology. . 1993; 13(9): 5567-81.
Koehler CM, Lindber GL, BrownDR, Beitz DC, Freeman AE, Mayfield JE and Myers AM Replacement of bovine mitochondrial DNA by a sequence variant within a single generation. Genetics 1991; 129: 247-255.