Rebuttal from Florian Lang and Else K. Hoffmann

Läng, Florian; Hoffmann, Else K.

doi:10.1113/jphysiol.2013.265231

Cited by 2 publications

(2 citation statements)

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“…In programmed CD, cell shrinkage is characteristic (though not universal) of apoptosis and in its initial phase accomplished by RVD-like cellular exit of ions, termed apoptotic volume decrease (AVD). In contrast, cell swelling is characteristic of necrosis and ischemic cell death/onkosis (derived from the Greek word ó γκ o ς , i.e., tumor/swelling Von Recklinghausen, 1910 ; Majno and Joris, 1995 ; Weerasinghe and Buja, 2012 ), termed necrotic volume increase (NVI) ( Okada et al, 2001 ; Orlov and Hamet, 2004 ; Lang and Hoffmann, 2012 , 2013a , b ; Orlov et al, 2013 ; Bortner and Cidlowski, 2014 , 2020 ; Model, 2014 ; Okada, 2020 ), and related modes of CD such as secondary necrosis, pyroptosis, or ferroptosis ( Zong and Thompson, 2006 ; D’Arcy, 2019 ; Nirmala and Lopus, 2020 ; Riegman et al, 2020 ). In methousis, not only is cell shrinkage absent but cells actually are swollen ( Overmeyer et al, 2008 ), such as seen in cells expressing an activated form of the H-Ras G12V oncoprotein (see below) ( Maltese and Overmeyer, 2014 ; Alonso-Curbelo et al, 2015 ).…”

Section: Cell Volume Regulationmentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

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The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.

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Section: Cell Volume Regulationmentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

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“…Similar increases in cell volume are prominent in several other related modes of CD, such as secondary necrosis (aponecrosis), pyroptosis, and ferroptosis (Formigli et al, 2000 ; Zong and Thompson, 2006 ; Silva, 2010 ; D'Arcy, 2019 ; Okada et al, 2019 ; Nirmala and Lopus, 2020 ; Riegman et al, 2020 ). While necrosis was initially considered to be a result of uncontrolled water accumulation, recent studies suggest that this form of CD starts with tightly controlled normotonic cell swelling, termed necrotic volume increase (NVI) (Barros et al, 2001 ; Okada et al, 2001 , 2021 ; Orlov and Hamet, 2004 ; Lang and Hoffmann, 2013a , b ; Orlov et al, 2013a , b ; Bortner and Cidlowski, 2014 ; Model, 2014 ; Bortner and Cidlowski ). In contrast, the highly regulated mode of CD, apoptosis, is generally associated with cell volume decrease (Majno and Joris, 1995 ; Lang et al, 1998 ; Maeno et al, 2000 ; Hoffmann et al, 2009 ).…”

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confidence: 99%