Mitochondrial dynamics and pore formation in regulated cell death pathways

Abstract

Mitochondria act as central hubs for cell death signaling. During apoptosis and regulated necrosis (pyroptosis, necroptosis, and ferroptosis), mitochondria undergo drastic changes including membrane permeabilization, fragmentation, and loss of membrane potential. However, dissection of the mechanisms underlying these processes is challenging because they involve remodeling of mitochondrial membranes coupled to the assembly of protein complexes whose dynamics are difficult to capture. We discuss progress in our understanding of mitochondrial alterations in cell death and highlight state-of-the-art experimental approaches to study them. We focus on advanced single-molecule and correlative microscopy methods which have recently provided unprecedented details about the dynamics and structure of protein complexes in mitochondria and their impact on membrane organization.

Keywords: apoptosis; correlative microscopy; mitochondria dynamics; mitochondrial outer membrane permeabilization (MOMP); pore formation; single-molecule microscopy.