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Senior Investigator

Richard J. Youle, Ph.D.

Biochemistry Section

Porter Neuroscience Research Center
Building 35 Room 2C-917
35 Convent Drive MSC 3704
Bethesda MD 20892-3704
Office: (301) 496-6628
Lab: (301) 496-6628
Fax: (301) 402-0380
YouleR@ninds.nih.gov

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 engineering new cell-type-specific protein toxins. He joined the Surgical Neurology Branch of NINDS in 1985 as a principal investigator where he has developed and moved into clinical trials new treatment strategies for brain tumors. His lab subsequently explored the molecular mechanisms of programmed cell death showing how Bcl-2 family members participate with mitochondria to control cell survival. Most recently his lab has discovered functions and interrelationships among proteins mutated in familial Parkinson’s disease. His current work focuses on molecular mechanisms of autophagy, mitochondrial quality control and neurodegenerative disorders.



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.

Staff Image
  • Nick Ader, B.S.
    Graduate Student

  • Heather Baldwin, M.A.
    Graduate Student

  • Eric Bunker, Ph.D.
    Postdoctoral Fellow

  • Tara Fischer, Ph.D.
    Postdoctoral Fellow

  • Ling Hao, Ph.D.
    Visiting Postdoctoral Fellow

  • Gil Kanfer, Ph.D.
    Visiting Postdoctoral Fellow

  • François Le Guerroue, Ph.D.
    Visiting Postdoctoral Fellow

  • Jose Noberto (Jobert) Vargas, Ph.D.
    Graduate Student

  • Shireen Sarraf, Ph.D.
    Postdoctoral Fellow

  • Shiori Sekine, Ph.D.
    Visiting Postdoctoral Fellow

  • Hetal Shah, B.S.
    Graduate Student

  • Danielle Sliter, Ph.D.
    Postdoctoral Fellow

  • Sue Smith, B.S.
    Laboratory Manager

  • Jose Noberto (Jobert) Vargas, B.S.
    Graduate Student

  • Chunxin (Black) Wang, Ph.D.
    Staff Scientist

  • 1) Yamano K, Wang C, Sarraf SA, Munch C, Kikuchi R, Noda NN, Hizukuri Y, Kanemaki MT, Harper JW, Tanaka K, Matsuda N, Youle RJ (2018)
  • Endosomal Rab cycles regulate Parkin-mediated mitophagy
  • eLife pii: e31326, doi: 10.7554/eLife.31326
  • 2) Sliter DA, Martinez J, Hao L, Chen X, Sun N, Fischer TD, Burman JL, Li Y, Zhang Z, Narendra DP, Cai H, Borsche M, Klein C, Youle RJ (2018)
  • Parkin and PINK1 mitigate STING-induced inflammation
  • Nature, 561, 258–262
  • 3) Burman JL, Pickles S, Wang C, Vargas J, Sekine S, Zhang Z, Nezich C, Youle AM, Wu Z, Hammer JA and Youle RJ (2017)
  • Mitochondrial Fission Facilitates the Selective Mitophagy of Protein Aggregates
  • J. Cell Biol, 216, 3231-3247
  • 4) Pickrell AM, Huang CH, Kennedy SR, Ordureau A, Sideris DP, Hoekstra JG, Harper JW, Youle RJ (2015)
  • Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons following Mitochondrial DNA Mutagenic Stress.
  • Neuron, 87, 371-81
  • 5) Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ. (2015)
  • The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy.
  • Nature, 524, 309-14
  • 6) Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ. (2014)
  • PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity.
  • Journal of Cell Biology, 205, 143-53
  • 7) Hasson SA, Kane LA, Yamano K, Huang C-H, Sliter DA, Buehler E, Wang C, Heman- Ackah SM, Hessa T, Guha R, Martin SE, Youle RJ (2013)
  • Genome-wide high-content RNAi screens identify regulators of Parkin upstream of mitophagy
  • Nature, 504, 291-295
  • 8) 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
  • 9) 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
  • 10) Narendra D, Jin S, Tanaka A, Suen DF, Gautier C, Shen J, Cookson M, Youle RJ (2010)
  • PINK1 is selectively stabilized on impaired mitochondria to trigger Parkin recruitment
  • PLoS Biol, 8, e1000298
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