Skip secondary menu

Biochemistry Section - Division of Intramural Research


Richard J. Youle Image

Richard J. Youle, Ph.D., Senior Investigator

Dr. Youle received an A.B. degree from Albion College and his Ph.D. degree from the University of South Carolina where he worked on the protein toxin ricin. He joined the lab of David Neville at the National Institute of Mental Health for postdoctoral work on the engineering of new cell-type-specific protein toxins. He joined the Surgical Neurology Branch of NINDS in 1985 as a principal investigator where he has developed new treatment strategies for brain tumors. His lab is now exploring the molecular mechanisms of programmed cell death and engineering therapeutic proteins to regulate cell survival.

Laboratory Staff

Soojay Banerjee, Ph.D.
Joan Barrick, B.S., Research Assistant
Adam Fogel, Ph.D., Postdoctoral Fellow
Sam Hasson, Ph.D., Postdoctoral Fellow
Chiu-Hui Huang, Ph.D., Postdoctoral Fellow
Seok-Min Jin, Ph.D., Postdoctoral Fellow
Alicia Pickrell, Ph.D., Postdoctoral Fellow
Jeni Sideris, Ph.D., Postdoctoral Fellow
Sue Smith, B.S., Research Assistant
Chunxin Wang, Ph.D., Postdoctoral Fellow
Koji Yamano, Ph.D., Postdoctoral Fellow
Richard J. Youle Staff Image

Research Interests

Programmed cell death. Neurons are programmed to die in great numbers during normal human development and aberrantly die by apoptosis in several neurodegenerative disorders. We are exploring the molecular mechanism of apoptosis concentrating on the roles of mitochondria and the Bcl-2 family of proteins. We have found that Bcl-xL and Bax move from the cytosol compartment to the mitochondria during apoptosis and that this step critically commits cells to the death pathway. Two major aspects of this process are under investigation; the molecular trigger for Bax migration into mitochondria and the consequences of Bax insertion into mitochondria. Live cell imaging of mitochondria and Bcl-2 family members analyzed by confocal microscopy has been instrumental in recent studies that link mitochondrial division processes to Bax mediated apoptosis. Unexpectedly, Bcl-2 family proteins have been found to regulate mitochondrial morphogenesis in healthy cells leading us to actively study the roles of mitochondrial fission and fusion especially in relation to neurodegenerative diseases.

Mitochondrial Quality Control. Mitochondria rapidly divide and fuse to form a dynamic network in cells. This process is essential for organelle quality control as evidenced by human neurodegenerative diseases caused by mutations in the genes of two large GTPases that mediate these processes. We have identified a series of E3 ligases on the outer mitochondrial membrane and are exploring how they control mitochondrial morphogenesis, protein turnover, and apoptosis.


Selected Recent Publications

  • Yamano K, Fogel AI, Wang C, van der Bliek AM, Youle RJ
    Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy, Elife, 2014, vol. 3, pp. e01612.. Full Text/Abstract
  • Hasson SA, Kane LA, Yamano K, Huang CH, Sliter DA, Buehler E, Wang C, Heman-Ackah SM, Hessa T, Guha R, Martin SE, Youle RJ
    High –content genome-wide RNAi screens identify regulators of Parkin upstream of mitophagy, Nature, 2013, vol. 504, pp. 291-5. Full Text/Abstract
  • Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ
    Pink1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding, J Cell Biol, 2013, vol. 200, pp. 163-72.. Full Text/Abstract
  • Youle RJ, van der Bliek AM
    Mitochondrial fission, fusion, and stress, Science, 2012, vol. 337, pp. 1062-5.
  • Lazarou M, Jin SM, Kane LA, Youle RJ
    Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin, Dev Cell, 2012, vol. 22, pp. 320-33.
  • Youle RJ, Narendra DP
    Mechanisms of mitophagy, Nat Rev Mol Cell Biol 12: 9-14, 2011
  • Edlich F, Banerjee S, Suzuki M, Cleland MM, Arnoult D, Wang C, Neutzner A, Tjandra N, and Youle, RJ
    Bclxl Retrotranslates Bax from the Mitochondria into the Cytosol, Cell 145: 104-116, 2011
  • Suen D-F, Narandra DP, Tanaka A, Manfredi G, Youle RJ
    Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells, PNAS 107: 11835-11840, 2010

Selected Earlier Publications


Contact Information

Surgical Neurology Branch, NINDS
Porter Neuroscience Research Center
Building 35, Room 2C-917
35 Convent Drive, MSC 3704
Bethesda, MD 20892-3704

Telephone: 301-496-6628 (office), 301-496-6628 (laboratory), 301-402-0380 (fax)
Email: youle@helix.nih.gov