English
norskBlar i forfatter "Deretic, Vojo"
Viser treff 1-7 av 7
-
ATG9A protects the plasma membrane from programmed and incidental permeabilization.
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-12)The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation ... -
Autophagy in major human diseases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-30)Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction ... -
Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-18)Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill‐defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3‐interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8‐SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate ... -
Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-29)The functions of mammalian Atg8 proteins (mATG8s) expand beyond canonical autophagy and include processes collectively referred to as Atg8ylation. Global modulation of protein synthesis under stress conditions is governed by MTOR and liquid-liquid phase separated condensates containing ribonucleoprotein particles known as stress granules (SGs). We report that lysosomal damage induces SGs acting as ... -
Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-28)Syntaxin 17 (Stx17) has been implicated in autophagosome-lysosome fusion. Here, we report that Stx17 functions in assembly of protein complexes during autophagy initiation. Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13<sup>+</sup>FIP200<sup>+</sup> mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 ... -
Stress granules and mTOR are regulated by membrane atg8ylation during lysosomal damage
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022)We report that lysosomal damage is a hitherto unknown inducer of stress granule (SG) formation and that the process termed membrane atg8ylation coordinates SG formation with mTOR inactivation during lysosomal stress. SGs were induced by lysosomedamaging agents including SARS-CoV-2ORF3a, Mycobacterium tuberculosis, and proteopathic tau. During damage, mammalian ATG8s directly interacted with the ... -
TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019-12-02)The tripartite motif (TRIM) proteins constitute a family of ubiquitin E3 ligases involved in a multitude of cellular processes, including protein homeostasis and autophagy. TRIM32 is characterized by six protein–protein interaction domains termed NHL, various point mutations in which are associated with limb-girdle-muscular dystrophy 2H (LGMD2H). Here, we show that TRIM32 is an autophagy substrate. ...
