Identifying specific receptors for cargo-mediated autophagy

Abstract

Macroautophagy has been implicated in numerous diseases, yet our understanding of the proteins responsible for the turnover of specific cargo by autophagy is limited. In a recent paper published in Nature, Mancias et al. used quantitative proteomics to identify a cohort of autophagosome-enriched proteins, one of which, nuclear receptor coactivator 4 (NCOA4) was shown to be required for the selective delivery of ferritin to the lysosome, ultimately regulating intracellular iron by autophagic turnover of ferritin, or ferritinophagy.

Figure 1

Identification of autophagy-associated proteins and protein interaction of top HCIP: NCOA4. (A) Workflow of autophagy-associated protein identification. (B) Different complex interactions of NCOA4 with HERC2, NEURL4, and the ferritin complex. Arrows depict the directionality of interaction with line weight indicating the weighted and normalized D score (WDN). Dotted lines represent data from the STRING database. Numbers in parentheses are the log₂(H:L) ratio obtained from A.