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

Area of Science:

• Cell Biology
• Physiology
• Biochemistry

Background:

• Cell volume (CV) is regulated by osmoregulatory processes.
• Pinocytosis involves rapid fluid and membrane uptake, yet cells maintain stable volume.
• Cell death pathways alter CV, with apoptosis decreasing it and necrosis increasing it.

Purpose of the Study:

• To explore the ionic mechanisms underlying cell volume regulation (CVR) and vesicular volume regulation (VVR).
• To understand the non-apoptotic cell death pathway, methuosis, characterized by excessive fluid accumulation via macropinocytosis.
• To elucidate how disruptions in CVR and VVR contribute to methuosis.

Main Methods:

• Review of ion and water transport mechanisms in cell volume regulation.
• Analysis of vesicular trafficking and the changing composition of ion channels and transporters.
• Examination of the interplay between ions, membranes, phosphoinositides, G proteins, and the cytoskeleton.

Main Results:

• Methuosis results from dysfunctional macropinocytosis, where macropinosomes fail to recycle/fuse with lysosomes, instead forming giant vacuoles.
• These giant vacuoles lead to plasma membrane rupture and cell death.
• Changes in vesicular ion concentrations and acidification during trafficking are crucial for macropinosome processing and shrinkage.

Conclusions:

• Understanding the ionic basis of CVR and VVR is critical for comprehending methuosis.
• Derangements in cellular mechanisms involving ion transport, vesicular dynamics, and cytoskeletal interactions can trigger methuotic cell death.
• This review highlights key cellular components and processes implicated in methuosis.