Koehler, Carla M.

Biochemistry

Website

Home URL

Division

Biochemistry

Title

Faculty
Professor

Specialties

Aging and Development
Biochemistry
Chemical Biology
Metabolism
Systems Biology and Biological Regulation

koehlerc@chem.ucla.edu

Office

Young Hall 4041A

Office Phone

(310) 794-4834

Lab

Young Hall 4043

Office Lab

(310) 825-8427

Biography

Carla M. Koehler is an American biochemist and professor at UCLA. Her research considers mitochondria and the processes which import proteins to their appropriate locations in the organelles. She was elected Fellow of the American Association for the Advancement of Science in 2018.

Koehler was a postdoctoral researcher at the Biozentrum University of Basel, where she studied the processes by which proteins enter mitochondria, in the laboratory of Gottfried Schatz. During her postdoctoral research, she worked on multi-protein complexes of the translocase of the outer membrane. She identified several novel translocase of the inner membrane proteins by developing temperature sensitive mutants.

In 1999, Koehler joined the Molecular Biology Institute at UCLA. Koehler makes use of genetics and biochemistry to understand the biogenesis of mitochondria. She has extensively investigated the import pathways of the translocase of the inner membrane (TIM) and translocase of the outer membrane (TOM) complexes. By understanding these biological pathways, Koehler looks to better understand the dysfunction in mitochondria that can give rise to disease.

Research Interests

Mitochondrial Biogenesis – Protein Translocation into Mitochondria

Our research encompasses two major areas: Understanding the mechanism of protein import into mitochondria and determining the process by which defects in mitochondrial protein translocation lead to disease.

A basic question in 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.

Representative Publications

Below is the list of the selected and most recent publications. For the full list, please visit here.

2015

The great escape: Mgr2 of the mitochondrial TIM23 translocon is a gatekeeper tasked with releasing membrane proteins. Steffen, J. and C.M. Koehler. 2015. Mol. Cell 56:613-614.
Mitochondria-targeted RNA import. Wang, G., E. Shimada, M. Nili, C. M. Koehler, and M.A. Teitell. 2015. Methods Mol. Biol. 1264:107-116. In Weissig, V. and Edeas, M., eds.: Springer’s Methods in Molecular Biology Mitochondrial Medicine, 2015.
Mia40 protein serves as an electron sink in the Mia40-Erv1 import pathway. Neal SE., Dabir DV., Tienson HL., Horn DM., Glaeser K., Ogozalek Loo RR., Barrientos A., Koehler C.M. . 2015. J Biol Chem 290(34): 2080-14

2014

Pharmacologic rescue of an enzyme-trafficking defect in primary hyperoxaluria 1. Miyata N, Steffen J, Johnson ME, Fargue S, Danpure CJ, Koehler CM. Proc Natl Acad Sci U S A. 2014 Sep 18. pii: 201408401. [Epub ahead of print] PMID: 25237136
TMEM14C is required for erythroid mitochondrial heme metabolism. Yien YY, Robledo RF, Schultz IJ, Takahashi-Makise N, Gwynn B, Bauer DE, Dass A, Yi G, Li L, Hildick-Smith GJ, Cooney JD, Pierce EL, Mohler K, Dailey TA, Miyata N, Kingsley PD, Garone C, Hattangadi SM, Huang H, Chen W, Keenan EM, Shah DI, Schlaeger TM, DiMauro S, Orkin SH, Cantor AB, Palis J, Koehler CM, Lodish HF, Kaplan J, Ward DM, Dailey HA, Phillips JD, Peters LL, Paw BH. J Clin Invest. 2014 Oct 1;124(10):4294-304. doi: 10.1172/JCI76979. Epub 2014 Aug 26. PMID: 25157825
Defining the role of oxygen tension in human neural progenitor fate. Xie, Y., J. Zhang, Y. Lin, X. Gaeta, X. Meng, D. R. Wisidagama, J. Cinkornpumin, C. M. Koehler, C. S. Malone, M. A. Teitell, and W. E. Lowry. 2014. Stem Cell Reports 3:743-757.

2013

The Taz1p transacylase is imported and sorted into the outer mitochondrial membrane via a membrane anchor domain. Herndon JD, Claypool SM, Koehler CM. Eukaryot Cell. 2013 Dec;12(12):1600-8.
Macrocytic anemia and mitochondriopathy resulting from a defect in sideroflexin 4. Hildick-Smith GJ, Cooney JD, Garone C, Kremer LS, Haack TB, Thon JN, Miyata N, Lieber DS, Calvo SE, Akman HO, Yien YY, Huston NC, Branco DS, Shah DI, Freedman ML, Koehler CM, Italiano JE Jr, Merkenschlager A, Beblo S, Strom TM, Meitinger T, Freisinger P, Donati MA, Prokisch H, Mootha VK, DiMauro S, Paw BH. Am J Hum Genet. 2013 Nov 7;93(5):906-14.
Meiosis I arrest abnormalities lead to severe oligozoospermia in meiosis 1 arresting protein (M1ap)-deficient mice. Arango NA, Li L, Dabir D, Nicolau F, Pieretti-Vanmarcke R, Koehler C, McCarrey JR, Lu N, Donahoe PK. Biol Reprod. 2013 Mar 28;88(3):76.
New tools for the identification of developmentally regulated enhancer regions in embryonic and adult zebrafish. Levesque MP, Krauss J, Koehler C, Boden C, Harris MP. Zebrafish. 2013 Mar;10(1):21-9.
A small molecule inhibitor of redox-regulated protein translocation into mitochondria. Dabir DV, Hasson SA, Setoguchi K, Johnson ME, Wongkongkathep P, Douglas CJ, Zimmerman J, Damoiseaux R, Teitell MA, Koehler CM. Dev Cell. 2013 Apr 15;25(1):81-92.

2012

Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. Zhang J, Nuebel E, Daley GQ, Koehler CM, Teitell MA. Cell Stem Cell. 2012 Nov 2;11(5):589-95.
A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss. von Ameln S, Wang G, Boulouiz R, Rutherford MA, Smith GM, Li Y, Pogoda HM, Nürnberg G, Stiller B, Volk AE, Borck G, Hong JS, Goodyear RJ, Abidi O, Nürnberg P, Hofmann K, Richardson GP, Hammerschmidt M, Moser T, Wollnik B, Koehler CM, Teitell MA, Barakat A, Kubisch C. Am J Hum Genet. 2012 Nov 2;91(5):919-27.
Role of twin Cys-Xaa9-Cys motif cysteines in mitochondrial import of the cytochrome C oxidase biogenesis factor Cmc1. Bourens M, Dabir DV, Tienson HL, Sorokina I, Koehler CM, Barrientos A. J Biol Chem. 2012 Sep 7;287(37):31258-69.
Measuring energy metabolism in cultured cells, including human pluripotent stem cells and differentiated cells. Zhang J, Nuebel E, Wisidagama DR, Setoguchi K, Hong JS, Van Horn CM, Imam SS, Vergnes L, Malone CS, Koehler CM, Teitell MA. Nat Protoc. 2012 May 10;7(6):1068-85.
Correcting human mitochondrial mutations with targeted RNA import. Wang G, Shimada E, Zhang J, Hong JS, Smith GM, Teitell MA, Koehler CM. Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4840-5.
The complexity of cardiolipin in health and disease. Claypool SM, Koehler CM. Trends Biochem Sci. 2012 Jan;37(1):32-41.

2011

UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. Zhang J, Khvorostov I, Hong JS, Oktay Y, Vergnes L, Nuebel E, Wahjudi PN, Setoguchi K, Wang G, Do A, Jung HJ, McCaffery JM, Kurland IJ, Reue K, Lee WN, Koehler CM, Teitell MA. EMBO J. 2011 Nov 15;30(24):4860-73.
PNPASE and RNA trafficking into mitochondria. Wang G, Shimada E, Koehler CM, Teitell MA. Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):998-1007. Review.
Barth syndrome mutations that cause tafazzin complex lability. Claypool SM, Whited K, Srijumnong S, Han X, Koehler CM. J Cell Biol. 2011 Feb 7;192(3):447-62.

2010

PNPASE regulates RNA import into mitochondria. Wang G, Chen HW, Oktay Y, Zhang J, Allen EL, Smith GM, Fan KC, Hong JS, French SW, McCaffery JM, Lightowlers RN, Morse HC 3rd, Koehler CM, Teitell MA. Cell. 2010 Aug 6;142(3):456-67.
The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model. Curado S, Ober EA, Walsh S, Cortes-Hernandez P, Verkade H, Koehler CM, Stainier DY. Dis Model Mech. 2010 Jul-Aug;3(7-8):486-95.
MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria. Zaltsman Y, Shachnai L, Yivgi-Ohana N, Schwarz M, Maryanovich M, Houtkooper RH, Vaz FM, De Leonardis F, Fiermonte G, Palmieri F, Gillissen B, Daniel PT, Jimenez E, Walsh S, Koehler CM, Roy SS, Walter L, Hajnóczky G, Gross A. Nat Cell Biol. 2010 Jun;12(6):553-62.
Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation. Hasson SA, Damoiseaux R, Glavin JD, Dabir DV, Walker SS, Koehler CM. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9578-83.

2009

Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Area-Gomez E, de Groof AJ, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA. Am J Pathol. 2009 Nov;175(5):1810-6.
Importing mitochondrial proteins: machineries and mechanisms. Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N. Cell. 2009 Aug 21;138(4):628-44.
Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins. Tienson HL, Dabir DV, Neal SE, Loo R, Hasson SA, Boontheung P, Kim SK, Loo JA, Koehler CM. Mol Biol Cell. 2009 Aug;20(15):3481-90.
Functional characterization of a mitochondrial Ser/Thr protein phosphatase in cell death regulation. Lu G, Sun H, Korge P, Koehler CM, Weiss JN, Wang Y. Methods Enzymol. 2009;457:255-73.
Redox regulation of protein folding in the mitochondrial intermembrane space.Koehler CM, Tienson HL. Biochim Biophys Acta. 2009 Jan;1793(1):139-45.

2008

The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome. Claypool SM, Boontheung P, McCaffery JM, Loo JA, Koehler CM. Mol Biol Cell. 2008 Dec;19(12):5143-55.
The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23. Beverly KN, Sawaya MR, Schmid E, Koehler CM. J Mol Biol. 2008 Oct 24;382(5):1144-56.
Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. Claypool SM, Oktay Y, Boontheung P, Loo JA, Koehler CM. J Cell Biol. 2008 Sep 8;182(5):937-50.
Gazing at translocation in the mitochondrion. Walsh S, Koehler CM. Cell. 2008 Aug 8;134(3):382-3.
Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. Gebert N, Chacinska A, Wagner K, Guiard B, Koehler CM, Rehling P, Pfanner N, Wiedemann N. EMBO Rep. 2008 Jun;9(6):548-54.

2007

Human polynucleotide phosphorylase: location matters. Chen HW, Koehler CM, Teitell MA. Trends Cell Biol. 2007 Dec;17(12):600-8.
A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1. Dabir DV, Leverich EP, Kim SK, Tsai FD, Hirasawa M, Knaff DB, Koehler CM. EMBO J. 2007 Nov 28;26(23):4801-11.
Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L, and DRP2 genes. Sedivá A, Smith CI, Asplund AC, Hadac J, Janda A, Zeman J, Hansíková H, Dvoráková L, Mrázová L, Velbri S, Koehler C, Roesch K, Sullivan KE, Futatani T, Ochs HD. J Clin Immunol. 2007 Nov;27(6):640-6.
Tim54p connects inner membrane assembly and proteolytic pathways in the mitochondrion. Hwang DK, Claypool SM, Leuenberger D, Tienson HL, Koehler CM. J Cell Biol. 2007 Sep 24;178(7):1161-75.
The function of TIM22 in the insertion of inner membrane proteins in mitochondria Oktay Y, Rainey RN, Koehler CM. In Dalbey, R. E., Koehler, C. M., and Tamanoi, F. (eds.) 2007 The Enzymes: Molecular Machines Involved in Protein Transport across Membrane. 25:367-386.
The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity. French SW, Dawson DW, Chen HW, Rainey RN, Sievers SA, Balatoni CE, Wong L, Troke JJ, Nguyen MT, Koehler CM, Teitell MA. Cancer Lett. 2007 Apr 18;248(2):198-210.
A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Lu G, Ren S, Korge P, Choi J, Dong Y, Weiss J, Koehler C, Chen JN, Wang Y. Genes Dev. 2007 Apr 1;21(7):784-96.
In vitro analysis of yeast mitochondrial protein import. Stuart RA, Koehler CM. Curr Protoc Cell Biol. 2007 Mar;Chapter 11:Unit 11.19.

2006

Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis. Chen HW, Rainey RN, Balatoni CE, Dawson DW, Troke JJ, Wasiak S, Hong JS, McBride HM, Koehler CM, Teitell MA, French SW. Mol Cell Biol. 2006 Nov;26(22):8475-87.
A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space. Rainey RN, Glavin JD, Chen HW, French SW, Teitell MA, Koehler CM. Mol Cell Biol. 2006 Nov;26(22):8488-97.
Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins. Claypool SM, McCaffery JM, Koehler CM. J Cell Biol. 2006 Jul 31;174(3):379-90.
Redox pathways of the mitochondrion.Koehler CM, Beverly KN, Leverich EP. Antioxid Redox Signal. 2006 May-Jun;8(5-6):813-22. Review.

2005

Hereditary spastic paraplegia: respiratory choke or unactivated substrate? Claypool SM, Koehler CM. Cell. 2005 Oct 21;123(2):183-5.
Protein translocation across membranes. Koehler CM, Hwang DK. In Meyers, R. A. (ed.), Encyclopedia of Molecular Cell Biology and Molecular Medicine 2005. Wiley-VCH, Weinheim, Vol. 11, pp. 287-308.
Patterns that define the four domains conserved in known and novel isoforms of the protein import receptor Tom20. Likic VA, Perry A, Hulett J, Derby M, Traven A, Waller RF, Keeling PJ, Koehler CM, Curran SP, Gooley PR, Lithgow T. J Mol Biol. 2005 Mar 18;347(1):81-93.

2004

EDITED BOOKS

Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development. Curran SP, Leverich EP, Koehler CM, Larsen PL. J Biol Chem. 2004 Dec 24;279(52):54655-62.
New developments in mitochondrial assembly.Koehler CM. Annu Rev Cell Dev Biol. 2004;20:309-35. Review.
Mitochondrial biogenesis. Protein import into and across the inner membrane. Curran SP, Koehler CM. In Koehler, C.M. and Bauer, M.F. (eds.), Topics in Current Genetics: Mitochondrial Function and Biogenesis 2004 Springer-Verlag, Heidelberg, Vol. 8, pp. 59-80.
The role of Hot13p and redox chemistry in the mitochondrial TIM22 import pathway. Curran SP, Leuenberger D, Leverich EP, Hwang DK, Beverly KN, Koehler CM. J Biol Chem. 2004 Oct 15;279(42):43744-51.
The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex. Roesch K, Hynds PJ, Varga R, Tranebjaerg L, Koehler CM. Hum Mol Genet. 2004 Sep 15;13(18):2101-11.
The small Tim proteins and the twin Cx3C motif.Koehler CM. Trends Biochem Sci. 2004 Jan;29(1):1-4. Review.
Structure, bioenergetics, and biogenesis of mitochondria. Leuenberger D, Curran SP, and Koehler CM. In Mullins, C. (ed.) The Biogenesis of Cellular Organelles 2004. Landes Bioscience, Georgetown, pp138-163.
Topics in Current Genetics: Mitochonrial Function and Biogenesis. Koehler, CM, Bauer MF (eds.) Springer-Verlag, Heidelberg, Vol 8, pp. 333.
The Enzymes: Molecular Machines Involved in Protein Transport accross Membranes. . Dalbey RE, Koehler CM Tamanoi F. (eds.) Elsevier, Oxford, Vol. 25, pp. 635

The Koehler Research Lab