Biochemistry Section - Division of Intramural Research

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
Sam Hasson, Ph.D., Postdoctoral Fellow
Chiu-Hui Huang, Ph.D., Postdoctoral Fellow
Seok-Min Jin, Ph.D., Postdoctoral Fellow
Sue Smith, B.S., Research Assistant
Chunxin Wang, 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

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
Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ
Proteosome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin, J Cell Biol 191:1367-80, 2010
Narendra DP, Jin SM, Tanaka A, Suen D-F, Gautier CA, Shen J, Cookson MR, Youle RJ
Pink is selectively stabilized on impaired mitochondria to activate Parkin, PLoBiol 8, e1000298, 2010
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
Suen D-F, Norris KL, Youle RJ
Mitochondrial dynamics and apoptosis, Genes Dev., 2008, vol. 22:1577-90

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