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Comment
. 2024 Oct;96(5):1120-1122.
doi: 10.1038/s41390-024-03382-2. Epub 2024 Jul 16.

Autophagy-related proteins measured in umbilical blood cord samples from human newborns: what can we learn from?

Affiliations
Comment

Autophagy-related proteins measured in umbilical blood cord samples from human newborns: what can we learn from?

Vanessa Ginet et al. Pediatr Res. 2024 Oct.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Overview of mammalian autophagy.
Autophagy involves the sequestration of cargos (such as long-lived proteins, organelles, and pathogens) by an intermediate multi-membrane organelle called the autophagosome, which then fuses with a lysosome to form an autolysosome for degradation. Autophagy can be divided into 4 main steps: induction/nucleation, elongation/incurvation, closure and maturation. Autophagy is induced by different cell stresses (such as starvation, oxidative stress, accumulation of defective proteins or unfunctional organelles) and depends on several protein complexes (not exhaustively represented in this figure). The PI3K-III (class III phosphoinositide 3-kinase)/BECN1 (BECLIN 1) complex drives the nucleation of the isolation membrane. Autophagosome membrane components could have different sources such as ER omegasome, mitochondria-associated membrane, trans-Golgi network (TGN) or plasma membrane. PI3K-III activation and generation of phosphatidylinositol 3-phosphate (PI3P) on isolation membrane serves as a signal for protein assembly required for autophagosome formation. LC3-II is a key autophagic protein playing important roles in elongation, cargo selection, incurvation, and closure steps of autophagy. A LC3 cytosolic precursor is first post-translationally modified (LC3-I) and then covalently conjugated to the membrane phospholipid phosphatidylethanolamine (PE) (LC3-II). This lipidated form is recruited at the phagophore membrane and remains on autophagosome membrane until maturation into a degradative autolysosome (acidification and loading in hydrolases). Fusion machinery involves RAB proteins (mainly RAB7) which recruit tethering complexes (HOPS, TECPR1) to bring the two vesicular compartments close enough to allow SNARE proteins to drive the fusion. SIRT1 is a NAD+-dependent histone deacetylase involved in various processes, including cell proliferation, survival, differentiation, oxidative stress, and autophagy. SIRT1 has been shown to regulate autophagy at different steps (induction, elongation and fusion). SQSTM1/p62 is an important autophagy receptor recruiting many cargoes (ubiquitinated substrates, mitochondria, bacteria…) into autophagosomes, and selectively degraded by autophagy.

Comment on

  • Differences in autophagy marker levels at birth in preterm vs. term infants.
    Künstle N, Gorlanova O, Marten A, Müller L, Sharma P, Röösli M, Sinues P, Schär P, Schürmann D, Rüttimann C, Da Silva Sena CR, Nahum U, Usemann J, Steinberg R, Yammine S, Schulzke S, Latzin P, Frey U; BILD study group. Künstle N, et al. Pediatr Res. 2024 Oct;96(5):1299-1305. doi: 10.1038/s41390-024-03273-6. Epub 2024 May 29. Pediatr Res. 2024. PMID: 38811718 Free PMC article.

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