PUBLICATION
Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy
- Authors
- Bertino, F., Zanin Venturini, D.I., Grasso, E., Kopecka, J., Salio, C., Gnutti, B., Basnet, R.M., Bellini, S., Mignani, L., Zhao, B., Kleefeld, F., Hentschel, A., Magnani, F., Fiorito, V., Abalai, R.E., Metani, L., Allocco, A.L., Petrillo, S., De Giorgio, F., Ammirata, G., Salsano, E., Pareyson, D., di Rocco, M., Abicht, A., McCourt, E., Horvath, R., Kölbel, H., Larson, A., Roos, A., Yu, T.W., Finazzi, D., Riganti, C., Tolosano, E., Chiabrando, D.
- ID
- ZDB-PUB-260215-4
- Date
- 2026
- Source
- Communications biology 9: 429 (Journal)
- Registered Authors
- Finazzi, Dario, Horvath, Rita
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 41691085 Full text @ Commun Biol
Citation
Bertino, F., Zanin Venturini, D.I., Grasso, E., Kopecka, J., Salio, C., Gnutti, B., Basnet, R.M., Bellini, S., Mignani, L., Zhao, B., Kleefeld, F., Hentschel, A., Magnani, F., Fiorito, V., Abalai, R.E., Metani, L., Allocco, A.L., Petrillo, S., De Giorgio, F., Ammirata, G., Salsano, E., Pareyson, D., di Rocco, M., Abicht, A., McCourt, E., Horvath, R., Kölbel, H., Larson, A., Roos, A., Yu, T.W., Finazzi, D., Riganti, C., Tolosano, E., Chiabrando, D. (2026) Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy. Communications biology. 9:429.
Abstract
Genetic pain loss disorders represent a heterogeneous group of rare diseases mainly characterized by defective nociception. Understanding the underlying molecular mechanism is fundamental to improve the treatment of patients affected by these rare disorders. Feline Leukemia Virus Subgroup C Receptor 1 (FLVCR1) is one of the genes previously associated with sensory neuropathy that requires further investigation. Here, we report on two additional patients with novel disease-causing variants in FLVCR1 and introduce a zebrafish model of the disease. The analyses of patient-derived fibroblasts show that distinct FLVCR1 variants compromised all the known functions associated with FLVCR1, thus affecting choline levels, heme biosynthesis and mitochondrial Ca2+ handling. Furthermore, we provide evidence that the alteration of these processes impairs the TCA cycle and OXPHOS, and induces lipid peroxidation. Our data points to the alterations of energetic metabolism as a potential driving pathomechanism in FLVCR1-associated sensory neuropathy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping