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Chi-yu Fu｜Institute of Cellular and Organismic Biology, Academia Sinica

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  • Chi-yu Fu Professor Chi-yu Fu ORCID
    Assistant Research Fellow
    • Specialty3D electron microscopy cellular structural biology structural biology
    • E-mailfuchiyu@gate.sinica.edu.tw
    • Tel02-2789-9565
    • Website Dr. Chi-yu Fu's Lab CHI-YU FU LAB
    • LabR425/ICOB
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Professional ExperienceOpenClose
2008-2013
Postdoctoral Fellow, Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute
2007-2008
Postdoctoral Fellow, Dept. of Microbiology, University of Alabama at Birmingham
2001-2006
Ph.D. in Biochemistry and Molecular Genetics, University of Alabama at Birmingham
Research InterestOpenClose

We use integrated 3DEM approaches to understand mitochondrial structure and network remodeling mechanisms. Mitochondria regulate cellular homeostasis and cell fate. They contain cristae membranes specialized for respiratory function. Cristae structure undergoes remodeling in physiology and pathology. The mechanisms of how it is regulated by cristae shaping proteins are not fully understood. In cells, mitochondria travel on microtubules and function as an integrated network that undergoes dynamic morphology reshaping through membrane fusion and fission processes. Miro is a critical Ca2+-dependent regulator of network homeostasis and the mutations are associated with Parkinson’s Disease (PD). However, how PD-associated Miro mutations affect network homeostasis is not clear at the molecular level. 

We develop EM and cryo-EM methods to study mitochondrial structural biology at multi-scales (Fig 1). We develop serial-section electron tomography and sample preparation methods to study ultrastructural phenotypes in large 3D volumes. We develop cryo-electron tomography and sample preparation methods to study how the cristae-shaping protein ATP synthase remodels cristae for cell functions in bioenergetics, steroidogenesis, adipogenesis, and mitochondrial permeability transition. We apply cryo-EM single-particle analysis to study how PD-associated Miro mutations disrupt mitochondrial network dynamics and transport by elucidating the complex structures with MFN and TRAK proteins. Using multi-scale 3DEM methods, the obtained cellular and molecular structural insights will help us tackle mitochondrial-related diseases. 

In the published works, we used these 3DEM methods to elucidate the regulation of cristae biogenesis, cristae bioenergetic enhancement, cristae shaping by MICOS, and its link with muscle development. In addition, we elucidate the regulation of mtDNA and mtNucleiod integrity and its connection with aging in Drosophila (Fig 2). We also elucidated the regulation of network reshaping by Ca2+-dependent Miro regulation of MFN-mediated fusion and elucidate the link in folliculogenesis and luteal formation in the ovarian cycle (Fig 3). 

Selected PublicationOpenClose
  1. Fatiga, F.F., Wang, L.J., Hsu, T., Capuno, J.I., and Fu, C.Y.* (2021). Miro1 functions as an inhibitory regulator of MFN at elevated mitochondrial Ca2+ levels. J Cell Biochem.
  2. Jiang, Y.F., Yu, P.H., Budi, Y.P., Chiu, C.H., and Fu, C.Y. (2021). Dynamic changes in mitochondrial 3D structure during folliculogenesis and luteal formation in the goat large luteal cell lineage. Sci Rep-Uk 11. (Contributions: project design, writing, and resources.) 
  3. Wang, L.J., Hsu, T., Lin, H.L., and Fu, C.Y.* (2021). Modulation of mitochondrial nucleoid structure during aging and by mtDNA content in Drosophila Biol Open. 
  4. Wang, L.J., Hsu, T., Lin, H.L., and Fu, C.Y.* (2020). Drosophila MICOS knockdown impairs mitochondrial structure and function and promotes mitophagy in muscle tissue. Biol Open 9.
  5. Jiang, Y.F., Lin, H.L., Wang, L.J., Hsu, T., and Fu, C.Y.* (2020). Coordinated organization of mitochondrial lamellar cristae and gain of COX function during mitochondrial maturation in Drosophila. Mol Biol Cell 31, 18-26
  6. Jiang, Y.F., Lin, H.L., and Fu, C.Y.* (2017). 3D Mitochondrial Ultrastructure of Drosophila Indirect Flight Muscle Revealed by Serial-section Electron Tomography. J Vis Exp. 
  7. Jiang, Y.F., Lin, S.S., Chen, J.M., Tsai, H.Z., Hsieh, T.S., and Fu, C.Y.* (2017). Electron tomographic analysis reveals ultrastructural features of mitochondrial cristae architecture which reflect energetic state and aging. Sci Rep 7, 45474.
  8. Veesler, D., Ng, T.S., Sendamarai, A.K., Eilers, B.J., Lawrence, C.M., Lok, S.M., Young, M.J., Johnson, J.E., and Fu, C.Y.* (2013). Atomic structure of the 75 MDa extremophile Sulfolobus turreted icosahedral virus determined by CryoEM and X-ray crystallography. Proceedings of the National Academy of Sciences of the United States of America 110, 5504-5509.
  9. Fu, C.Y., K. Wang, L. Gan, J. Lanman, R. Khayat, M. J. Young, G. J. Jensen, P. C. Doerschuk and J. E. Johnson (2010). "In vivo assembly of an archaeal virus studied with whole-cell electron cryotomography." Structure 18(12): 1579-1586.
  10. Fu, C.Y., C. Uetrecht, S. Kang, M. C. Morais, A. J. Heck, M. R. Walter and P. E. Prevelige, Jr. (2010). "A docking model based on mass spectrometric and biochemical data describes phage packaging motor incorporation." Mol Cell Proteomics 9(8): 1764-1773.