Melanocytes-A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy

Camilla Pellegrini, Alessandra Zulian, Francesca Gualandi, Elisa Manzati, Luciano Merlini, Maria E. Michelini, Luisa Benassi, Sandra Marmiroli, Alessandra Ferlini, Patrizia Sabatelli, Paolo Bernardi, Nadir M. Maraldi

Research output: Contribution to journalArticle

Abstract

Dystrophin is a subsarcolemmal protein that, by linking the actin cytoskeleton to the extracellular matrix via dystroglycans, is critical for the integrity of muscle fibers. Here, we report that epidermal melanocytes, obtained from conventional skin biopsy, express dystrophin with a restricted localization to the plasma membrane facing the dermal-epidermal junction. In addition the full-length muscle isoform mDp427 was clearly detectable in melanocyte cultures as assessed by immunohistochemistry, RNA, and Western blot analysis. Melanocytes of Duchenne muscular dystrophy (DMD) patients did not express dystrophin, and the ultrastructural analysis revealed typical mitochondrial alterations similar to those occurring in myoblasts from the same patients. Mitochondria of melanocytes from DMD patients readily accumulated tetramethylrhodamine methyl ester, indicating that they are energized irrespective of the presence of dystrophin but, at variance from mitochondria of control donors, depolarized upon the addition of oligomycin, suggesting that they are affected by a latent dysfunction unmasked by inhibition of the ATP synthase. Pure melanocyte cultures can be readily obtained by conventional skin biopsies and may be a feasible and reliable tool alternative to muscle biopsy for functional studies in dystrophinopathies. The mitochondrial dysfunction occurring in DMD melanocytes could represent a promising cellular biomarker for monitoring dystrophinopathies also in response to pharmacological treatments.

Original languageEnglish
Pages (from-to)1323-1331
Number of pages9
JournalJournal of Cellular Physiology
Volume228
Issue number6
DOIs
Publication statusPublished - Jun 2013

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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  • Cite this

    Pellegrini, C., Zulian, A., Gualandi, F., Manzati, E., Merlini, L., Michelini, M. E., Benassi, L., Marmiroli, S., Ferlini, A., Sabatelli, P., Bernardi, P., & Maraldi, N. M. (2013). Melanocytes-A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy. Journal of Cellular Physiology, 228(6), 1323-1331. https://doi.org/10.1002/jcp.24290