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Biochemistry Section

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.

Staff:

• Soojay Banerjee, Ph.D., 301-433-0148 banerjees@ninds.nih.gov
• Joan Barrick, B.S., Research Assistant, 301-435-3634 barrickj@ninds.nih.gov
• Adam Fogel, Postdoctoral Fellow, 301-435-3633 fogelai@ninds.nih.gov
• Sam Hasson, Ph.D., Postdoctoral Fellow, 301-594-2631 hassons@mail.nih.gov
• Chiu-Hui Huang, Ph.D., Postdoctoral Fellow, 301-451-1718 huangC2@ninds.nih.gov
• Seok-Min Jin, Ph.D., Postdoctoral Fellow, 301-435-3637 Jins2@ninds.nih.gov
• Lesley Kane , Postdoctoral Fellow, 301-451-1716 kanela@ ninds.nih.gov
• Michael Lazarou, Postdoctoral Fellow, 301-594-1230 lazaroum@ ninds.nih.gov
• Alicia Pickrell, Postdoctoral Fellow, 301-435-3632 pickrellam@mail.nih.gov
• Jenni Sideris, Postdoctoral Fellow, 301-496-2061 siderispd@mail.nih.gov
• Danielle Sliter, Postdoctoral Fellow, 301-451-1719 sliterda@mail.nih.gov
• Sue Smith, B.S., Research Assistant, 301-480-3540 SueSmith@ninds.nih.gov
• Chunxin Wang, Ph.D., Postdoctoral Fellow, 301-496-6820 wangchu@ninds.nih.gov
• Koji Yamano, Postdoctoral Fellow, 301-451-1717 yamanok@mail.nih.gov

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 Publications:

• Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress, Science 337, 1062-5.
• Lazarou M, Jin SM, Kane LA, Youle RJ (2012) Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin, Dev Cell 22, 320-33.
• Youle RJ, Narendra DP (2011) Mechanisms of mitophagy, Nat Rev Mol Cell Biol 12: 9-14 .
• Edlich F, Banerjee S, Suzuki M, Cleland MM, Arnoult D, Wang C, Neutzner A, Tjandra N, and Youle, RJ (2011) Bclxl Retrotranslates Bax from the Mitochondria into the Cytosol, Cell 145: 104-116 .
• Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteosome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin, J Cell Biol 191:1367-80 .
• Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) Pink is selectively stabilized on impaired mitochondria to activate Parkin, PLoBiol 8, e1000298 .
• Suen D-F, Narandra DP, Tanaka A, Manfredi G, Youle RJ (2010) Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells, PNAS 107: 11835-11840 .

All Selected Publications

Contact Information:
Dr. Richard J. Youle
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