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.,  ,  301 433 0148
Joan Barrick,  B.S.,  Research Assistant,  301 435 3634
Adam Fogel,  Postdoctoral Fellow,  301 435 3633
Sam Hasson,  Ph.D.,  Postdoctoral Fellow,  301 594 2631
Tara Hessa,  Postdoctoral Fellow,  301 496 2061
Chiu-Hui Huang,  Ph.D.,  Postdoctoral Fellow,  301 435 3633
Chiu-Hui Huang,  Ph.D.,  Postdoctoral Fellow,  301 451 1718
Seok-Min Jin,  Ph.D.,  Postdoctoral Fellow,  301 435 3637
Lesley  Kane ,  Postdoctoral Fellow,  301 451 1716
Michael Lazarou,  Postdoctoral Fellow,  301 594 1230
Danielle Sliter,  Postdoctoral Fellow,  301 451 1719
Sue Smith,  B.S.,  Research Assistant,  301 480 3540
Chunxin  Wang,  Ph.D.,  Postdoctoral Fellow,  301 496 6820
Koji Yamano,  Postdoctoral Fellow,  301 451 1717

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

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, 

Youle RJ, Narendra DP
Mechanisms of mitophagy - Nat Rev Mol Cell Biol 12: 9-14    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, 

Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ
Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL - J Cell Biol 191: 933-942    2010, 

Youle RJ, Strasser A
The BCL-2 protein family: opposing activities that mediate cell death - Nat Rev Mol Cell Biol 9: 47-59     2008, 

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