Cloud hunting: doryphagy, a form of selective autophagy that degrades centriolar satellites

Abstract

The selective clearance of cellular components by macroautophagy (hereafter autophagy) is critical for maintaining cellular homeostasis. In this punctum, we summarize and discuss our recent findings regarding a novel type of selective autophagy that targets centriolar satellites (CS) for degradation, a process we termed doryphagy from the Greek word "doryphoros", standing for "satellite". CS are microtubule-associated protein complexes that regulate centrosome composition. We show that CS degradation is mediated through a direct interaction between GABARAPs and an LC3-interacting region (LIR) motif in the CS protein PCM1. Autophagy-deficient systems accumulate large abnormal CS and consequently display centrosome reorganization and abnormal mitoses. Our findings provide a mechanistic link between autophagy deficiency and centrosome abnormalities and exemplify how mammalian Atg8-family proteins (mATG8s) can regulate substrate specificity.

Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling

“…How precisely autophagy modulates cilia formation, length, and maintenance remain incompletely resolved. Nevertheless, emerging evidence suggests that the balance between autophagy and proteasomal degradation influences cilia formation and resorption as well as the maintenance of centrioles and basal bodies (Boukhalfa et al, 2019;Holdgaard et al, 2020;Izawa et al, 2015;Liang et al, 2016;Paridaen et al, 2013).…”

Xenopus epidermal and endodermal epithelia as models for mucociliary epithelial evolution, disease, and metaplasia

“…Primary cilia formation is induced upon serum starvation, which inhibits mTORC1 and promotes autophagy (Boukhalfa, Miceli, Ávalos, Morel, & Dupont, 2019). On the other hand, proteasomal degradation promotes cilia resorption and elimination of centriole and basal body proteins (Boukhalfa et al, 2019; Holdgaard, Cianfanelli, & Cecconi, 2020; Izawa, Goto, Kasahara, & Inagaki, 2015; Liang, Meng, Zhu, & Pan, 2016; Paridaen, Wilsch‐Bräuninger, & Huttner, 2013). Interestingly, the roles of autophagy and the use of Rapamycin have been considered in the context of COPD and Asthma, were tested in various models, but with variable effects (Kennedy & Pennypacker, 2016; Lam et al, 2013; Mitani, Ito, Vuppusetty, Barnes, & Mercado, 2016; Mushaben, Kramer, Brandt, Khurana Hershey, & le Cras, 2011; Wang et al, 2018).…”

Centrosome instability: when good centrosomes go bad

“…For instance, centrosome amplification can interrupt autophagosome trafficking, disrupting autophagy and preventing degradation of autophagic targets [ 222 ]. Conversely, disrupting selective autophagy of centrosome components – a process known called doryphagy – causes centrosome fragmentation and disruption [ 223 ]. Additionally, the centrosome has recently been implicated in organization of the actin cytoskeleton, including concentrating the actin regulator LIM Kinase 1 during mitosis [ 224 , 225 ].…”