Mitochondria in Neurodegeneration

 

Principal Investigator

 

Prof. Dr. Stephan Frank

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Group Members

 

Lara Sironi

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Our Science

 

Our lab focuses on the molecular mechanisms of mitochondrial dynamics and their role in neuronal health and pathophysiology. As particularly energy-dependent cells, neurons rely on balanced mitochondrial fusion and fission processes. Using primary neuronal cultures and inducible neuron-specific knockout models of the mitochondrial fission protein DRP1 as experimental tools, we recently found that genetic ablation of mitochondrial fission in forebrain neurons causes defects in synaptic transmission and memory functions. In addition, CNS-specific Drp1 ablation also activates interorganellar signaling cascades. Further pursuing this aspect, we currently study the crosstalk of mitochondria with the endoplasmic reticulum, with a special focus on Parkinson’s disease.

 

Selected Publications

  • Sironi L, Restelli LM, Tolnay M, Neutzner A, Frank S. Dysregulated Interorganellar Crosstalk of Mitochondria in the Pathogenesis of Parkinson's Disease. Cells. 2020.
  • Shahmoradian SH, Lewis AJ, Genoud C, et al. Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes. Nat Neurosci. 2019.
  • Gill JF, Delezie J, Santos G, et al. Peroxisome proliferator-activated receptor γ coactivator 1α regulates mitochondrial calcium homeostasis, sarcoplasmic reticulum stress, and cell death to mitigate skeletal muscle aging. Aging Cell. 2019.
  • Akbergenov R, Duscha S, Fritz AK, et al. Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations. EMBO Rep. 2018.
  • Huang X, Wu BP, Nguyen D, et al. CHCHD2 accumulates in distressed mitochondria and facilitates oligomerization of CHCHD10. Hum Mol Genet. 2018.
  • Bento AC, Bippes CC, Kohler C, Hemion C, Frank S, Neutzner A. UBXD1 is a mitochondrial recruitment factor for p97/VCP and promotes mitophagy. Sci Rep. 2018.
  • Restelli LM, Oettinghaus B, Halliday M, et al. Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21. Cell Rep. 2018.
  • Schmitt K, Grimm A, Dallmann R, et al. Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics. Cell Metabol. 2018.
  • Oettinghaus B, Schulz JM, Restelli LM, et al. Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death Differ. 2016.
  • Oettinghaus B, D'Alonzo D, Barbieri E, et al. DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress. BBA Bioenergetics. 2016.
  • Ackema KB, Prescianotto-Baschong C, Hench J, et al. Sar1, a Novel Regulator of ER-Mitochondrial Contact Sites. PLOS One. 2016.
 

Awards and Grants

  • Bangerter Foundation (2017-2019)
  • Mach-Gaensslen Foundation (2018-2021)
  • Novartis Foundation for Medical-Biological Research (2019-2020)