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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

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.
    Postdoctoral Fellow

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

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

  • Sarah Pickles, Ph.D.
    Postdoctoral Fellow

  • Shireen Sarraf, Ph.D.
    Postdoctoral Fellow

  • Hetal Shah, B.S.
    Graduate Student

  • Danielle Sliter, Ph.D.
    Postdoctoral Fellow

  • Sue Smith, B.S.
    Laboratory Manager

  • 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) Nezich CL, Wang C, Fogel AI, Youle RJ. (2015)
  • MiT/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5
  • Journal of Cell Biology, 210, 435-50
  • 6) 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
  • 7) Yamano K, Fogel AI, Wang C, van der Bliek AM, Youle RJ (2014)
  • Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy
  • Elife, 3, e01612.
  • 8) 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
  • 9) 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
  • 10) Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ (2013)
  • Pink1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding
  • J Cell Biol, 200, 163-72.
  • 11) 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 (2013)
  • High –content genome-wide RNAi screens identify regulators of Parkin upstream of mitophagy
  • Nature, 504, 291-5
  • 12) 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
  • 13) Youle RJ, van der Bliek AM (2012)
  • Mitochondrial fission, fusion, and stress
  • Science, 337, 1062-5
  • 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
  • 15) Youle RJ, Narendra DP (2011)
  • Mechanisms of mitophagy
  • Nat Rev Mol Cell Biol 12: 9-14
  • 16) Edlich F, Banerjee S, Suzuki M, Arnoult D, Cleland M, Wang C, Neutzner A, Tjandra N, Youle RJ (2011)
  • Bcl-xL retrotranslocates Bax from mitochondria into the cytosol
  • Cell, 145, 104-116
  • 17) 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
  • 18) 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
  • 19) 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
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