Autophagosome Biogenesis

Abstract

Autophagy–the lysosomal degradation of cytoplasm–plays a central role in cellular homeostasis and protects cells from potentially harmful agents that may accumulate in the cytoplasm, including pathogens, protein aggregates, and dysfunctional organelles. This process is initiated by the formation of a phagophore membrane, which wraps around a portion of cytoplasm or cargo and closes to form a double-membrane autophagosome. Upon the fusion of the autophagosome with a lysosome, the sequestered material is degraded by lysosomal hydrolases in the resulting autolysosome. Several alternative membrane sources of autophagosomes have been proposed, including the plasma membrane, endosomes, mitochondria, endoplasmic reticulum, lipid droplets, hybrid organelles, and de novo synthesis. Here, we review recent progress in our understanding of how the autophagosome is formed and highlight the proposed role of vesicles that contain the lipid scramblase ATG9 as potential seeds for phagophore biogenesis. We also discuss how the phagophore is sealed by the action of the endosomal sorting complex, which is required for transport (ESCRT) proteins.

TheArabidopsis thalianaTRAPPIII subunit AtTRAPPC8/AtTRS85 is involved in ER functioning and autophagy

“…We considered then the possibility that elevated Dol levels result from reduced rates of dolichol degradation, but no specific mechanism of Dol degradation in cells has been described yet. We reasoned that, since dolichol resides in the ER membrane and the ER is likely an important source of membrane for autophagy (Zhen & Stenmark, 2023), a decrease in autophagic membrane turnover could be the underlying cause of decreased Dol degradation. To test this idea, we measured Dol levels in several homozygous atg mutants of A. thaliana : atg2 , atg5 , atg9 , atg11 , atg13 .…”

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

“…It is important to transport lipid droplets to lysosomes for degradation. 13,49 To investigate the effect of NPS BG @Cur on lipid droplet transportation, co-staining of ADFP and Lyso-tracker was performed (Fig. 5F-J).…”

Epigenetic targeting of autophagy for cancer: DNA and RNA methylation

“…The core of autophagy is the formation of double-membraned structures called autophagosomes, proficiently encapsulating cytoplasmic components, including organelles and proteins, marked for degradation ( 24 ). Subsequently, these autophagosomes merge with lysosomes, culminating in the formation of autolysosomes, wherein the engulfed material succumbs to the catabolic prowess of lysosomal hydrolases ( 25 , 26 ). The ensuing breakdown products are then carefully recycled back into the cytoplasm, providing crucial sustenance for energy production and macromolecular synthesis, thereby furnishing steadfast support to cellular function during periods of exigency ( 27 ) ( Figure 1A ).…”