Live Cell Imaging of ATP Levels Reveals Metabolic Compartmentalization within Motoneurons and Early Metabolic Changes in FUS ALS Motoneurons

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Vitaly L. Zimyanin - , University of Virginia, Technische Universität Dresden (Autor:in)
  • Anna Maria Pielka - , Universität Rostock (Autor:in)
  • Hannes Glaß - , Universität Rostock (Autor:in)
  • Julia Japtok - , Klinik und Poliklinik für Neurologie (Autor:in)
  • Dajana Großmann - , Universität Rostock (Autor:in)
  • Melanie Martin - , Institut für Physiologie (Autor:in)
  • Andreas Deussen - , Institut für Physiologie (Autor:in)
  • Barbara Szewczyk - , Universität Rostock (Autor:in)
  • Chris Deppmann - , University of Virginia (Autor:in)
  • Eli Zunder - , University of Virginia (Autor:in)
  • Peter M. Andersen - , Umeå University (Autor:in)
  • Tobias M. Boeckers - , Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE), Universität Ulm (Autor:in)
  • Jared Sterneckert - , Center for Regenerative Therapies Dresden (CRTD), Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Stefanie Redemann - , University of Virginia (Autor:in)
  • Alexander Storch - , Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE), Universität Rostock (Autor:in)
  • Andreas Hermann - , Universität Rostock, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (Autor:in)


Motoneurons are one of the most energy-demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultrastructure, transport, and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and the proper function of motor neurons. However, how changes in metabolic rates contribute to ALS progression is not fully understood yet. Here, we utilize hiPCS-derived motoneuron cultures and live imaging quantitative techniques to evaluate metabolic rates in fused in sarcoma (FUS)-ALS model cells. We show that differentiation and maturation of motoneurons are accompanied by an overall upregulation of mitochondrial components and a significant increase in metabolic rates that correspond to their high energy-demanding state. Detailed compartment-specific live measurements using a fluorescent ATP sensor and FLIM imaging show significantly lower levels of ATP in the somas of cells carrying FUS-ALS mutations. These changes lead to the increased vulnerability of diseased motoneurons to further metabolic challenges with mitochondrial inhibitors and could be due to the disruption of mitochondrial inner membrane integrity and an increase in its proton leakage. Furthermore, our measurements demonstrate heterogeneity between axonal and somatic compartments, with lower relative levels of ATP in axons. Our observations strongly support the hypothesis that mutated FUS impacts the metabolic states of motoneurons and makes them more susceptible to further neurodegenerative mechanisms.


PublikationsstatusVeröffentlicht - Mai 2023

Externe IDs

PubMed 37408187
ORCID /0000-0002-7688-3124/work/142250054



  • amyotrophic lateral sclerosis, metabolism, mitochondria, Mitochondria/metabolism, Humans, Adenosine Triphosphate/metabolism, Amyotrophic Lateral Sclerosis/metabolism, Mutation, Motor Neurons/metabolism, RNA-Binding Protein FUS/genetics