Ammonium the autophagosomes are not degraded before

Ammonium chloride (NH4Cl)
is as a well-known lysosomotropic autophagy inhibitor that alkalizes acidic pH.

NH4Cl acts by disturbing the endo/lysosomal and autophagy/lysosomal
pathway through neutralizing the low pH. This process inhibits degradation step
by blocking lysosomes. To measure autophagic flux, LC3 turnover assays are
established, which are based on the observation that LC3 is degraded in
autolysosomes. When cells are treated with autophagy inhibitors such as NH4Cl,
the degradation of LC3-II is blocked causing it accumulate. The differences in
the quantity of LC3-II between samples in the presence and absence of lysosomal
inhibitors represent the amount of LC3 which is delivered to lysosomes for
degradation, this what was described earlier as autophagic flux.

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Any autophagy inhibitor will
usually result in an increase in LC3-II puncta (Mizushima et al., 2010). To make sure that
the autophagosomes are not degraded before true LC3-II measurements are
established, this alkalization factor inhibits the autophagic pathway before
the degradation step. Given that autophagy is part of the cellular stress
response, it is not unexpected that this process can also influence decision
making on cell death (Martin,
2011, Muñoz-Pinedo and
Martin, 2014). In
fact, excessive autophagy leads to increased autophagosome synthesis and may be
associated with decreased lysosomal activity thus remain unfused, and their
accumulation is useless for autophagy. I one study it was found that
accumulation of autophagosomes compromised cell viability whereas experiments
with depleted autophagosomes did not (Robert W.) This can be compared to the
p53-dependent cell response, which is primarily concerned with coordinating DNA
damage-associated repair also resulting in apoptosis above a certain threshold
of p53 activation. This makes decent biological sense, as cells with extreme
DNA damage are unsafe to repair due to the potential for the development of
cancer. (Muñoz-Pinedo,)

Autosis is one of three types of cell death which are grouped based on
morphological criteria. Type I programmed cell death (apoptosis), type II
programmed cell death (Autosis or Autophagic-cell death), type III unprogrammed
cell death (necrosis), the latter being an uncontrolled and non-physiological
type of cellular death.

Autosis
is a non-apoptotic novel form of autophagy gene-dependent cell death, which is
mediated by the Na+, K+, ATPase pump. The morphological characteristics of this
cell death are predominantly enhanced cell-substrate adhesion, focal ballooning
of the perinuclear space, and dilation and disintegration of the endoplasmic
reticulum (ER). (Liu, Y, and B Levine. )

 This cell death occurs under certain
experimental conditions, triggered by treatment with autophagy-inducing
peptides, starvation and hypoxia and in vivo types of ischemia.

There
are contradictory reports that autophagy can be both oncogenic and tumor
suppressive. This presents a potential difficulty for using inhibitors of
autophagy to treat cancer among other diseases, as the effect of inhibiting
autophagy in different situations is hard to predict. (Macintosh, Robin L).