Dear Go J. Yoshida, 

The written contradictory phenomena of autophagy should be studied via comparing difference between molecular mechanism of autophagy and molecular mechanism of phagocytosis, considering also remote cellular reacrion across distance, due to cellular capacitors operation, which transit into contact reaction of the strange object disription by lysosome pathway. Can a dead cell turn into strange object?

Disturbed autophagy flux (all of p62/SQSTM1, LC3-II, and ubiquitinated proteins accumulate) and activation of caspase 3 (apoptosis) occurs before the cell death. The most concern is what induces apoptosis instead of autophagic cell death from the disrupted autophagy-lysosome pathway. 

I am sorry, but there are besides caspase 3 (apoptosis) the great Bcl-2 Family in which there are the proapoptotic factors [Bax, BAD, Bok and the other] and antiapoptotic factors [Bcl-2, Bcl-xL, Bcl-w and other]. All these factors operate in regulation the length of each cell life down to cell death inducing apoptosis, in spite to autophagy. However the remote cellular reactions across distance, due to cellular capacitors operation, occur via different mechanisms in these processes. Just now I try to explain these mechanisms from point of view of biophysics and thermodynamics.

Dear Dr. Mónica Suárez Korsnes.

Than you for the great paper.

Go 

 Dear Dr. Go J Yoshida

Our studies had similarly results as you found.

We found that GMI, a Ganoderma immunomodulatory protein, can enhance cisplatin-induced apoptosis. The results showed that 3-MA decreases, while chloroquine increases GMI and cisplatin cotreatment-induced apoptosis. Interestingly, 3-MA and shLC3 can reduce the chloroquine-enhanced apoptosis. 

In the recent publication, we found that FIP-gts, another Ganoderma immunomodulatory protein, induces caspase-independent cell death (CICD). Chloroquine can enhance the FIP-gts-induced CICD. ShLC3 inhibit FIP-gts and chloroquine-induced CICD.

We hypothesise that GMI and FIP-gts induced abundant autophagosome accumulation stress (referred to as AAA stress). However, we still don't know how it work.

I hope our studies can be useful.

I look forward to your study to answer this question.

Best regards

I-Lun

Article GMI, an Immunomodulatory Protein from Ganoderma microsporum ...

Article Immunomodulatory proteins FIP-gts and Chloroquine induce Cas...

Thank you for letting me know the very informative papers. Accumulated autophagosome accumulation stress induces caspase-independent cell death, probably "autophagic cell death," which is attenuated by the treatment with 3-MA. 

CICD shares several characteristics with apoptois, such as sub-G1 accumulation.  It was a mitochondria-mediated apoptosis-like cell death, so some paper also called it "caspase-independent apoptosis. The CICD can be activated by apoptosis-inducing stress under caspase-inhibiting condition, such as Bcl-2 activation. Therefore, we think that CICD is more like apoptosis and different from autophagic cell death.

 This type of cell death resulting from accumlated autophagosomes  may be called apoptosis with autophagic features.

Please see this publication by Narabayashi et al.2015: J Gastroenterol. 2015 May;50(5):541-54. doi: 10.1007/s00535-014-0995-2. Epub 2014 Sep 12.

Indomethacin suppresses LAMP-2 expression and induces lipophagy and lipoapoptosis in rat enterocytes via the ER stress pathway.

Please see this publication may be use full to you  by xuehua shao et al. 2016; 6: 35482. Published online 2016 Oct 18. doi: 10.1038/srep35482.

Induction of Autophagy and Apoptosis via PI3K/AKT/TOR Pathways by Azadirachtin A in Spodoptera litura Cells

I am attached here reprint

Best Regards 

Jalpa Raja