Membrane damage and repair: a thin line between life and death

Abstract

Bilayered membranes separate cells from their surroundings and form boundaries between intracellular organelles and the cytosol. Gated transport of solutes across membranes enables cells to establish vital ion gradients and a sophisticated metabolic network. However, an advanced compartmentalization of biochemical reactions makes cells also particularly vulnerable to membrane damage inflicted by pathogens, chemicals, inflammatory responses or mechanical stress. To avoid potentially lethal consequences of membrane injuries, cells continuously monitor the structural integrity of their membranes and readily activate appropriate pathways to plug, patch, engulf or shed the damaged membrane area. Here, we review recent insights into the cellular mechanisms that underly an effective maintenance of membrane integrity. We discuss how cells respond to membrane lesions caused by bacterial toxins and endogenous pore-forming proteins, with a primary focus on the intimate crosstalk between membrane proteins and lipids during wound formation, detection and elimination. We also discuss how a delicate balance between membrane damage and repair determines cell fate upon bacterial infection or activation of pro-inflammatory cell death pathways.

Keywords: Mycobacterium tuberculosis; ESCRT; cell death; lysosome; pore-forming proteins; sphingomyelin.