I am more clinician than a bench work scientist. However, in my bench work I strongly feel autophagy and apoptosis are in a continuum. I can not say necrosis, itself, is within this continuum or not since necrosis is not a programmed cell death. Necrosis is more like acute, not very well prepared, death. Necrosis does not involve ATP formation inside of the cells. I hope my limited knowledge can help you.

Probably and more!

To me autophagy is a mechanism that serve a purpose to keep cell alive in harsh environment but it is a process that can not be abused by the cell if the harshness lasts too long. Using endothelial cells from two different sites we saw a quite different behavior of autophagy with one pro-survival and the other pro-death. It may be contect related.

Many thanks, Doctor Ru-Jeng Teng!!!!!!!!!!!!!!

So, the inclination and predisposition and hence similarity of autophagy to apoptosis and necrosis may form a continuum!

I am more clinician than a bench work scientist. However, in my bench work I strongly feel autophagy and apoptosis are in a continuum. I can not say necrosis, itself, is within this continuum or not since necrosis is not a programmed cell death. Necrosis is more like acute, not very well prepared, death. Necrosis does not involve ATP formation inside of the cells. I hope my limited knowledge can help you.

Autophagy , apoptosis, and necrosis are three major types of programmed cell death

The semantics can be tricky. Strictly speaking, autophagy is a catabolic process by which cells break up damaged or non-critical components to enable survival in nutrient-starved conditions. Normally, this is a pro-survival mechanism.

For reasons still being clarified, this process may lead to cell death, with the characteristic stigmata of autophagy. This can be labelled as autophagic cell death, which indeed is apparently part of a continuum of programmed cell death with apoptosis on the other end of the spectrum.

This old paper gives a good overview of the morphology of cell death:

Majno, G. and I. Joris (1995). "Apoptosis, oncosis, and necrosis. An overview of cell death." Am J Pathol 146(1): 3-15.

This paper clarifies the terminology somewhat:

Kroemer, G., W. S. El-Deiry, et al. (2005). "Classification of cell death: recommendations of the Nomenclature Committee on Cell Death." Cell Death Differ 12 Suppl 2: 1463-1467.

Many thanks, Doctors Paresh Kulkarni, Lidia Mazur and Umar Wazir!!!!!!!!!!!!!!!!!

Autophagy is a type of programmed cell death

Three major modes of programmed cell death : apoptosis, necrosis and autophagy

I have read different opinion about necrosis as a form of programmed cell death. Necroptosis, subtype of necrosis, was found to be a kind of PCD but in general I learn necrosis is not. I know there will be debate about it but it should be an open discussion.

Many thanks Doctor Ru-Jeng Teng!!!!!!!!!!!!!!!!!!!!!

I agree!!!!!!!!!!!!!!!!!!!!!!

Dear Tobias: Isn't it fun to have discussions in science?

Absolutely, Doctor Ru-Jeng Teng!!!!!!!!!!!!!!!!

Dr. Teng, I agree we are learning from these questions. The homeostasis pattern of cell entropy brings in the self-perpetuating continuum of opposites aka the Kreb's cycle. The key, I think, is the direction (entropy) of the cells that determine apoptosis/necrosis influences on the cells. In acute, as you know, necrosis almost always is winning the battle. In chronic, apoptosis is holding its own, at best, but as the patient's biomarkers improve relative to a more robust Kreb's (citric acid) cycle that actually reaches the pH 7.45 and 100% oxygen potential, inflammation turns to anti-inflammatory cytokines and their health status will continue its path to optimal health. At least, that is the pattern we strive for in our consulting work in chronic disease.

Dear Dr. Chartrand: I totally agree. As a clinician I always feel cells or even animal will try to find the best way to survive. That may be the reason why we will get sometimes totally opposite response compare to in vitro studies. I have been asked numerous times by reviewers why two cell types in my animal model go opposite way? I do believe that is how the animal survives the harsh environment otherwise the animal will die before we are able to study it. The role of autophagy, apoptosis, and necrosis also depends on the context.

Excellent observations, Dr. Teng. Survival mechanisms do appear at the heart of these contradictory processes.

The programmed cell death network was shown in "Systems biology analysis of programmed cell death" published inTrends in Biochemical Sciences Vol. 35 No. 10 556-564.

Is autophagy a combination and/or hybrid of (elements of) apoptosis and necrosis?

NO !

Dear Lidia: I agree that autophagy is not a combination/hybrid of apoptosis and necrosis. They use different network but BECN-1 in involved, to some extent, in both autophagy and apoptosis. I have no doubt people may have difference takes in reading the literature and it is why we are eager to find out they interactions.

Sorry, it should BECN-1 not BECN-2. I hit the wrong key not intentionally.

Three main types of programmed cell death are distinguished: autophagy, apoptosis, and necrosis.

Your detailed answer is here.. :)

http://www.nature.com/cdd/journal/v19/n1/pdf/cdd201196a.pdf