Table 1.
Cellular Process | Key Player/s | Effect of Silencing | References |
---|---|---|---|
MVB Biogenesis | ESCRT-0 (HRS) ESCRT-I (TSG101) ESCRT-III/VPS4 |
HRS depletion: enlarged MVBs with few ILVs TSG101 depletion: MVB formation strongly reduced ESCRT-III/Vps24 depletion: smaller MVBs in clusters HRS TSG101, Vps22 and Vps24 co-depletion: MVBs and ILVs still formed |
[53,128,129,130] |
Autophagy | ESCRT-I (VPS37A) ESCRT-III (CHMP2A)/VPS4 |
VPS37A depletion: accumulation of phagophores due to defects in autophagosome completion CHMP2A depletion: accumulation of immature autophagosomal structures; impairment of autophagic flux; inhibition of phagophore sealing during mitophagy CHMP2A, CHMP3, CHMP7 depletion: increase in immature autophagosomal membranes under starvation CHMP2A, CHMP4B and VPS4 depletion: inhibition of mitophagy |
[66,67] |
Cytokinesis | ESCRT-I (TSG101)/ESCRT-II Alix ESCRT-III (CHMP-6,CHMP4B,CHMP4C)/VPS4 |
Alix depletion: an increase in multinuclear cells; furrow regression; a failure in CHMP4C recruitment to the midbody; CHMP4B still recruited TSG101 and Alix co-depletion: failure in CHMP4B recruitment to the midbody; multinucleation non aggravated Alix, VPS22, and CHMP6 co-depletion: CHMP4B is not recruited to the intercellular bridge CHMP4C depletion: altered cytokinetic arrest in the presence of chromosomal problems; furrow regression and binucleation |
[73,74,80,88,131] |
Cell Membrane Repair | ESCRT-I (TSG101) Alix ESCRT-III (CHMP4B)/VPS4 |
Alix, CHMP2B VPS4 depletion: failure of the repairing process followed by cell death (CHMP4B and VPS4 silencing) CHMP2A depletion: impairment of the repairing process CHMP3 depletion: no significant effect |
[99,101] |
Nuclear Membrane Repair | ESCRT-III (CHMP4B, CHMP7)/VPS4 | Alix, HD-PTP, HRS, TSG101 depletion: no effects on CHMP4B recruitment to the site of ruptures CHMP7depletion: failure of CHMP4B recruitment to the nuclear envelope |
[107,108] |
Lysosomal Membrane Repair | ESCRT-I (TSG101) Alix ESCRT-III (CHMP2A, CHMP4B)/VPS4 |
HRS depletion: no effect on CHMP4B recruitment to lysosomes TSG101 depletion: consistent delay in CHMP4B recruitment CHMP2A depletion: increased accumulation of CHMP4B on damaged lysosomes Alix depletion: no detectable effect on CHM4B recruitment TSG101 and Alix co-depletion: almost complete abrogation of CHMP4B recruitment; failure of recovering of damaged lysosomes |
[118,119] |