The Secrets of Alternative Autophagy

Abstract

For many years, it was thought that ATG5 and ATG7 played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells with ATG5 or ATG7 depletion still generate autophagic vacuoles with mainly trans-Golgi-originated isolation membranes and do not die. This indicates that autophagy can occur via ATG5/ATG7-independent alternative autophagy. Its molecular mechanism differs from that of the canonical pathway, including inter alia the phosphorylation of ULK1, and lack of LC3 modifications. As the alternative autophagy pathway has only recently been described, little is known of its precise role; however, a considerable body of evidence suggests that alternative autophagy participates in mitochondrion removal. This review summarizes the latest progress made in research on alternative autophagy and describes its possible molecular mechanism, roles and methods of detection, and possible modulators. There is a need for further research focused on types of autophagy, as this can elucidate the functioning of various cell types and the pathogenesis of human and animal diseases.

Ligustrazine and liguzinediol protect against doxorubicin‐induced cardiomyocytes injury by inhibiting mitochondrial apoptosis and autophagy

“…Both apoptosis and autophagy are types of cell death that are associated with the development of HF 4,8,9 . Autophagy is a cellular process whereby cytoplasmic components are sequestered within a bimembrane structure called an autophagosome and subsequently transported to the lysosome for degradation 10–12 . However, excessive or dysregulated autophagy can contribute to the development of several cardiovascular diseases.…”

Filter-aided extracellular vesicle enrichment (FAEVEr) for proteomics

“…), cells are known to upregulate autophagy related (ATG) proteins to replenish essential building blocks and release non-ESCRT dependent exosomes through the formation of autophagosomes (77), which can fuse with endosomes to form amphisomes, similar to MVBs. In addition, the ATG5-ATG16L complex (78,79) influences the EV secretion through dissociation of V-ATPases, thereby preventing MVB acidification and its subsequent lysosomal degradation (80,81). Ultimately, this promotes MVB fusion with the PM and secretion of the ILVs as exosomes.…”

Autophagy mediates cancer cell resistance to doxorubicin induced by the Programmed Death 1/Programmed Death Ligand 1 immune checkpoint axis

“…Beclin 1 is a component of class III PI3K complexes that produce phosphatidylinositol 3-phosphate [PI(3)P], which is essential for phagophore formation and the initiation of the autophagosome (20,22). Both Atg5 and Atg7 play important roles in the elongation and maturation of the autophagic membrane during canonical autophagy (23). However, cells can generate autophagic vacuoles via an alternative Atg5/Atg7-independent autophagy pathway (23).…”

“…Both Atg5 and Atg7 play important roles in the elongation and maturation of the autophagic membrane during canonical autophagy (23). However, cells can generate autophagic vacuoles via an alternative Atg5/Atg7-independent autophagy pathway (23). In our study, the fact that knockdown of either Beclin 1 or Atg7 resulted in the complete inhibition of rPD-1-mediated resistance to doxorubicin in 4T1 cells indicates that activation of the canonical autophagy pathway is required.…”