Self-eating in skeletal development: implications for lysosomal storage disorders.
Macroautophagy (a.k.a. autophagy) is a cellular process aimed at the recycling of proteins and organelles that is achieved when autophagosomes fuse with lysosomes. Accordingly, lysosomal dysfunctions are often associated with impaired autophagy. We demonstrated that inactivation of the sulfatase modifying factor 1 gene (Sumf1), a gene mutated in multiple sulfatase deficiency (MSD), causes glycosaminoglycans (GAGs) to accumulate in lysosomes, which in turn disrupts autophagy. We utilized a murine model of MSD to study how impairment of this process affects chondrocyte viability and thus skeletal development.
Settembre
Carmine
C
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. cs2545@columbia.edu
Arteaga-Solis
Emilio
E
Ballabio
Andrea
A
Karsenty
Gerard
G
D000818:Animals; D001343:Autophagy; D001846:Bone Development; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure; D016464:Lysosomal Storage Diseases / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013429:Sulfatases / Q000172:deficiency / Q000378:metabolism
D050862:Oxidoreductases Acting on Sulfur Group Donors; C519507:Sumf1 protein, mouse; D013429:Sulfatases