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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Vitaly L. Zimyanin - , University of Virginia, TUD Dresden University of Technology (Author)
  • Anna Maria Pielka - , University of Rostock (Author)
  • Hannes Glaß - , University of Rostock (Author)
  • Julia Japtok - , Department of Neurology (Author)
  • Dajana Großmann - , University of Rostock (Author)
  • Melanie Martin - , Institute of Physiology (Author)
  • Andreas Deussen - , Institute of Physiology (Author)
  • Barbara Szewczyk - , University of Rostock (Author)
  • Chris Deppmann - , University of Virginia (Author)
  • Eli Zunder - , University of Virginia (Author)
  • Peter M. Andersen - , Umeå University (Author)
  • Tobias M. Boeckers - , German Center for Neurodegenerative Diseases (DZNE), Ulm University (Author)
  • Jared Sterneckert - , Chair of iPS Cells and Neurodegenerative Diseases, Center for Regenerative Therapies Dresden, Medical Faculty Carl Gustav Carus (Author)
  • Stefanie Redemann - , University of Virginia (Author)
  • Alexander Storch - , German Center for Neurodegenerative Diseases (DZNE), University of Rostock (Author)
  • Andreas Hermann - , University of Rostock, German Center for Neurodegenerative Diseases (DZNE) (Author)


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.


Original languageEnglish
Article number1352
Issue number10
Publication statusPublished - May 2023

External 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

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