LC3 and GABARAP independent autophagy of misfolded procollagen in mouse osteoblasts.

ABSTRACT: Bone synthesis should depend on autophagy because over 10% of type I procollagen (PC1) - a heterotrimer of COL1A1 and COL1A2 chains and the precursor of the main bone matrix molecule - is misfolded and rerouted from osteoblast endoplasmic reticulum (ER) to lysosomes. However, osteoblast-specific macroautophagy knockouts in mice have produced only mild bone effects. To reconcile these observations, we compared how hypomorphic expression and a conditional knockout (cKO) of Atg5 - encoding a protein required for autophagosome formation - affected Col1a2^G610C/+ versus wild-type Col1a2^+/+ osteoblasts in vivo and in vitro. The Gly610-to-Cys substitution (G610C) in the triple helical region of the COL1A2/proα2(I) chain increases PC1 misfold

SUBMITTER: Makareeva E 

PROVIDER: S-EPMC12487762 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature