David Chan Research Group at Caltech

Molecular analysis of mitochondrial dynamics and membrane fusion

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For general information on mitochondrial dynamics:

Chan, D.C., and Carelli, V. (2014). Mitochondrial DNA: shaping life and death of neurons. Neuron, in press.

Mishra, P., and Chan, D.C. (2014). Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol 15, 634-646.

Chan, D.C. (2012). Fusion and fission: interlinked processes critical for mitochondrial health. Annual Review of Genetics 46, 265-287. [PDF]

Chen, H., and Chan, D.C. (2009). Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases. Hum Mol Genet 18, R169-176. [PDF]

Chan, D. C. (2006). Mitochondria: dynamic organelles in disease, aging, and development. Cell 125, 1241-1252. [PDF]

 

Selected Publications

Chan, D.C., and Carelli, V. (2014). Mitochondrial DNA: shaping life and death of neurons. Neuron, in press.

Mishra, P., and Chan, D.C. (2014). Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol 15, 634-646.

Mishra, P., Carelli, V., Manfredi, G., and Chan, D.C. (2014). Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metabolism 19, 630-641.

Loson, O.C., Liu, R., Rome, M.E., Meng, S., Kaiser, J.T., Shan, S.O., and Chan, D.C. (2014). The mitochondrial fission receptor MiD51 requires ADP as a cofactor. Structure 22, 367-377.

Ngo, H.B., Lovely, G.A., Phillips, R., and Chan, D.C. (2014). Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nature Communications 5, 3077.

Chan, N.C., den Besten, W., Sweredoski, M.J., Hess, S., Deshaies, R.J., and Chan, D.C. (2014). Degradation of the Deubiquitinating Enzyme USP33 Is Mediated by p97 and the Ubiquitin Ligase HERC2. J Biol Chem 289, 19789-19798.

Wang, Y.E., Marinov, G.K., Wold, B.J., and Chan, D.C. (2013). Genome-wide analysis reveals coating of the mitochondrial genome by TFAM. PloS One 8, e74513.

Loson, O.C., Song, Z., Chen, H., and Chan, D.C. (2013). Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 24, 659-667.

Kim, K.H., Jeong, Y.T., Oh, H., Kim, S.H., Cho, J.M., Kim, Y.N., Kim, S.S., Kim do, H., Hur, K.Y., Kim, H.K., et al. (2013). Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine. Nature medicine 19, 83-92.

Chan, D.C. (2012). Fusion and fission: interlinked processes critical for mitochondrial health. Annual Review of Genetics 46, 265-287. [PDF]

Pham, A.H., McCaffery, J.M., and Chan, D.C. (2012a). Mouse lines with photo-activatable mitochondria to study mitochondrial dynamics. Genesis 50, 833-843. [PDF]

Pham, A.H., Meng, S., Chu, Q.N., and Chan, D.C. (2012b). Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit. Hum Mol Genet 21, 4817-4826. [PDF]

Chan, D.C., and Schon, E.A. (2012). Eliminating mitochondrial DNA from sperm. Dev Cell 22, 469-470. [PDF]

Zhang, Y., Chan, N.C., Ngo, H.B., Gristick, H., and Chan, D.C. (2012). Crystal structure of mitochondrial fission complex reveals scaffolding function for mitochondrial division 1 (Mdv1) coiled coil. J Biol Chem 287, 9855-9861. [PDF]

Li, J., Liu, X., Wang, H., Zhang, W., Chan, D.C., and Shi, Y. (2012). Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression. Proc Natl Acad Sci U S A 109, 6975-6980.

Aravin, A.A., and Chan, D.C. (2011). piRNAs meet mitochondria. Dev Cell 20, 287-288. [PDF]

Chan, N.C., and Chan, D.C. (2011). Parkin uses the UPS to ship off dysfunctional mitochondria. Autophagy 7, 771-772. [PDF]

Ngo, H.B., Kaiser, J.T., and Chan, D.C. (2011). The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. Nature structural & molecular biology 18, 1290-1296. [PDF]

Chan, N.C., Salazar, A.M., Pham, A.H., Sweredoski, M.J., Kolawa, N.J., Graham, R.L., Hess, S., and Chan, D.C. (2011). Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 20, 1726-1737. [PDF]

Chen, H., Vermulst, M., Wang, Y.E., Chomyn, A., Prolla, T.A., McCaffery, J.M., Chan, D.C. (2010). Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutation. Cell 141, 280–289. [PDF]  

Ban, T., Heymann, JA., Song, Z., Hinshaw, JE., Chan, D.C. (2010). OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. Hum Mol Genet. [PDF]

Song, Z., Ghochani, M., McCaffery, J.M., Frey, T.G., and Chan, D.C. (2009). Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol Biol Cell 20, 3525-353. [PDF]

Detmer, S.A., Velde, C.V., Cleveland, D.W., and Chan, D.C. (2008). Hindlimb gait defects due to motor axon loss and reduced distal muscles in a transgenic mouse model of Charcot-Marie-Tooth type 2A. Hum Mol Genet 17, 367-375. [PDF]

Zhang, Y., and Chan, D.C. (2007). Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proc Natl Acad Sci U S A 104, 18526-18530. [PDF]

Detmer, S.A., and Chan, D.C. (2007). Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8, 870-879. [PDF]

Chen, H., McCaffery, J.M., and Chan, D.C. (2007). Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130, 548-562. [PDF]

Song, Z., Chen, H., Fiket, M., Alexander, C., and Chan, D.C. (2007). OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol 178, 749-755. [PDF]

Chan, D.C. (2007). Mitochondrial dynamics in disease. The New England Journal of Medicine 356, 1707-1709. [PDF]

Detmer, S. A., and Chan, D. C. (2007). Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol 176, 405-414. [PDF]

Chan, D. C. (2006). Mitochondria: dynamic organelles in disease, aging, and development. Cell 125, 1241-1252. [PDF]

Chan, D. C. (2006). Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22, 79-99. [PDF]

Griffin, E. E., Detmer, S. A., and Chan, D. C. (2006). Molecular mechanism of mitochondrial membrane fusion. Biochim Biophys Acta 1763, 482-489. [PDF]

Griffin, E. E., and Chan, D. C. (2006). Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion. J Biol Chem 281, 16599-16606. [PDF]

Chen, H., and Chan, D. C. (2005). Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14 Spec No. 2, R283-289. [PDF]

Griffin, E. E., Graumann, J., and Chan, D. C. (2005). The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J Cell Biol 170, 237-248. [PDF]

Chen, H., Chomyn, A., and Chan, D. C. (2005). Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280, 26185-26192. [PDF] [supplement]

Suntoke, T. R., and Chan, D. C. (2005). The fusion activity of HIV-1 gp41 depends on interhelical interactions. J Biol Chem 280, 19852-19857. [PDF]

Koshiba, T., Detmer, S. A., Kaiser, J. T., Chen, H., McCaffery, J. M., and Chan, D. C. (2004). Structural basis of mitochondrial tethering by mitofusin complexes. Science 305, 858-862. [PDF]

Karbowski, M., Arnoult, D., Chen, H., Chan, D. C., Smith, C. L., and Youle, R. J. (2004). Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. J Cell Biol 164, 493-499.

Chen, H., and Chan, D. C. (2004). Mitochondrial dynamics in mammals. Curr Top Dev Biol 59, 119-144. [PDF]

Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., and Chan, D. C. (2003). Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160, 189-200. [PDF]

Koshiba, T., and Chan, D. C. (2003). The prefusogenic intermediate of HIV-1 gp41 contains exposed C-peptide regions. J Biol Chem 278, 7573-7579. [PDF]

Chan, D. C., and Kim, P. S. (1998). HIV entry and its inhibition. Cell 93, 681-684. [PDF]

Chan, D. C., Chutkowski, C. T., and Kim, P. S. (1998). Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc Natl Acad Sci U S A 95, 15613-15617. [PDF]

Malashkevich, V. N., Chan, D. C., Chutkowski, C. T., and Kim, P. S. (1998). Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides. Proc Natl Acad Sci U S A 95, 9134-9139. [PDF]

Chan, D. C., Fass, D., Berger, J. M., and Kim, P. S. (1997). Core structure of gp41 from the HIV envelope glycoprotein. Cell 89, 263-273. [PDF]