Mitochondrial membrane tension governs fission

TLDR

Mitochondrial fission involves assembly of factors on the outer membrane that generate constriction, which can either divide or reverse, but the role of membrane tension in this process has remained undefined. The study aims to capture the dynamics of constricting mitochondria in mammalian cells using live‑cell structured illumination microscopy and a fluorescence lifetime‑based membrane tension sensor, and to propose a model linking tension and bending energy to constriction outcomes. Live‑cell structured illumination microscopy was employed to image constriction dynamics, while a fluorescence lifetime sensor quantified membrane tension, and the data were used to construct a model of tension‑dependent bending energy. Mitochondria are under tension, and when tension is reduced, constrictions initiate at the same rate but are less likely to divide.

Abstract

During mitochondrial fission, key molecular and cellular factors assemble on the outer mitochondrial membrane, where they coordinate to generate constriction. Constriction sites can eventually divide or reverse upon disassembly of the machinery. However, a role for membrane tension in mitochondrial fission, although speculated, has remained undefined. We capture the dynamics of constricting mitochondria in mammalian cells using live-cell structured illumination microscopy (SIM). By analyzing the diameters of tubules that emerge from mitochondria and implementing a fluorescence lifetime-based mitochondrial membrane tension sensor, we discover that mitochondria are indeed under tension. Under perturbations that reduce mitochondrial tension, constrictions initiate at the same rate, but are less likely to divide. We propose a model based on our estimates of mitochondrial membrane tension and bending energy in living cells which accounts for the observed probability distribution for mitochondrial constrictions to divide.