Gregory J Krause, Antonio Diaz, Maryam Jafari, Rabia R Khawaja, Esperanza Agullo-Pascual, Olaya Santiago-Fernández, Alicia L Richards, Kuei-Ho Chen, Phillip Dmitriev, Yan Sun, Stephanie K See, Kotb Abdelmohsen, Krystyna Mazan-Mamczarz, Nevan J Krogan, Myriam Gorospe, Danielle L Swaney, Simone Sidoli, Jose Javier Bravo-Cordero, Martin Kampmann, Ana Maria Cuervo
Autophagy is essential for protein quality control and regulation of the functional proteome. Failure of autophagy pathways with age contributes to loss of proteostasis in aged organisms and accelerates the progression of age-related diseases. In this work, we show that activity of endosomal microautophagy (eMI), a selective type of autophagy occurring in late endosomes, declines with age and identify the sub-proteome affected by this loss of function. Proteomics of late endosomes from old mice revealed an aberrant glycation signature for Hsc70, the chaperone responsible for substrate targeting to eMI...
September 18, 2022: Aging Cell