Starvation-induced autophagy occurs independently of the ATG1 complex in Chlamydomonas
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Abstract
The survival of eukaryotes during starvation depends on effective nutrient recycling via autophagy. Accordingly, loss of autophagy-related (ATG) proteins, including the nutrient-sensing ATG1 kinase complex, typically results in reduced fitness or lethality under nutrient limitation. The green alga Chlamydomonas reinhardtii provides a tractable model for autophagy studies, as its ATG repertoire is encoded by single-copy genes. Here, we generated a comprehensive library of ATG deletion mutants and examined their growth and autophagy during starvation. Surprisingly, starvation-induced autophagy occurred in the absence of ATG1 complex components (ATG1, ATG11, ATG13, and ATG101), revealing ATG1-independent autophagy and challenging the canonical model for autophagy initiation.
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Starvation-induced autophagy occurs independently of the ATG1 complex in Chlamydomonas
Here, you find that autophagic flux proceeds to completion in Chlamydomonas lacking ATG1 complex components, even under acute TOR inhibition, where the canonical mechanism runs directly through ATG1 kinase activity. This is a compelling result worth engaging with carefully.
The gene identifications here rely on sequence similarity and phylogenetic analysis, which establish orthology but not functional equivalence. Have the Chlamydomonas ATG1, ATG11, ATG13, and ATG101 proteins been shown to physically interact and form a kinase-active complex? Without that, another interpretation is available: if the complex has diverged structurally or catalytically in C. reinhardtii, its dispensability may simply reflect that the canonical ATG1 kinase function was …
Starvation-induced autophagy occurs independently of the ATG1 complex in Chlamydomonas
Here, you find that autophagic flux proceeds to completion in Chlamydomonas lacking ATG1 complex components, even under acute TOR inhibition, where the canonical mechanism runs directly through ATG1 kinase activity. This is a compelling result worth engaging with carefully.
The gene identifications here rely on sequence similarity and phylogenetic analysis, which establish orthology but not functional equivalence. Have the Chlamydomonas ATG1, ATG11, ATG13, and ATG101 proteins been shown to physically interact and form a kinase-active complex? Without that, another interpretation is available: if the complex has diverged structurally or catalytically in C. reinhardtii, its dispensability may simply reflect that the canonical ATG1 kinase function was already absent. The elevated basal ATG8-PE in ATG1 complex knockouts suggests these proteins are doing something regulatory, but that's consistent with either reading.
Something else must be relaying the TOR signal to the ATG8 lipidation machinery if ATG1 is not. The finding that PI3K remains required suggests it's not a completely orthogonal pathway. Have you considered a systematic approach, such as phosphoproteomics under AZD8055, to identify what TOR is actually targeting in Chlamydomonas when ATG1 is absent? The partial reduction in flux in atg13 and atg11 mutants relative to atg1 also suggests these proteins may have roles outside the canonical complex worth exploring.
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