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2014 ; 184
(6
): 1630-42
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Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome
and endosome compartments
#MMPMID24726643
Maltese WA
; Overmeyer JH
Am J Pathol
2014[Jun]; 184
(6
): 1630-42
PMID24726643
show ga
Apoptosis is the most widely recognized form of physiological programmed cell
death. During the past three decades, various nonapoptotic forms of cell death
have gained increasing attention, largely because of their potential importance
in pathological processes, toxicology, and cancer therapy. A recent addition to
the panoply of cell death phenotypes is methuosis. The neologism is derived from
the Greek methuo (to drink to intoxication) because the hallmark of this form of
cell death is displacement of the cytoplasm by large fluid-filled vacuoles
derived from macropinosomes. The demise of the cell resembles many forms of
necrosis, insofar as there is a loss of metabolic capacity and plasma membrane
integrity, without the cell shrinkage and nuclear fragmentation associated with
apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic
expression of activated Ras, but recent reports have described small molecules
that can induce the features of methuosis in a broad spectrum of cancer cells,
including those that are resistant to conventional apoptosis-inducing drugs. This
review summarizes the available information about the distinguishing
morphological characteristics and underlying mechanisms of methuosis. We compare
and contrast methuosis with other cytopathological conditions in which
accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we
highlight key questions that need to be answered to determine whether methuosis
truly represents a unique form of regulated cell death.