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 language | English |
|---|---|
| Pages (from-to) | 1323-1331 |
| Number of pages | 9 |
| Journal | Journal of Cellular Physiology |
| Volume | 228 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2013 |
Fingerprint
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
Cite this
Melanocytes-A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy. / Pellegrini, Camilla; Zulian, Alessandra; Gualandi, Francesca; Manzati, Elisa; Merlini, Luciano; Michelini, Maria E.; Benassi, Luisa; Marmiroli, Sandra; Ferlini, Alessandra; Sabatelli, Patrizia; Bernardi, Paolo; Maraldi, Nadir M.
In: Journal of Cellular Physiology, Vol. 228, No. 6, 06.2013, p. 1323-1331.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melanocytes-A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy
AU - Pellegrini, Camilla
AU - Zulian, Alessandra
AU - Gualandi, Francesca
AU - Manzati, Elisa
AU - Merlini, Luciano
AU - Michelini, Maria E.
AU - Benassi, Luisa
AU - Marmiroli, Sandra
AU - Ferlini, Alessandra
AU - Sabatelli, Patrizia
AU - Bernardi, Paolo
AU - Maraldi, Nadir M.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874199731&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874199731&partnerID=8YFLogxK
U2 - 10.1002/jcp.24290
DO - 10.1002/jcp.24290
M3 - Article
C2 - 23169061
AN - SCOPUS:84874199731
VL - 228
SP - 1323
EP - 1331
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 6
ER -