Mitochondrial dynamics and mechanosignalling - Integrating metabolic demand and life-death decisions with microenvironmental mechanics.

The way by which cells sense and interpret their microenvironment is fundamental to the regulation of their behaviour. Mechanosignalling is an essential aspect of microenvironmental sensing by cells, particularly within complex three-dimensional tissues, but it remains unclear how this signalling interacts with and modulates organelles such as mitochondria. Mitochondria form a dynamic network throughout the cytoplasm, intricately intertwined with the cytoskeleton and other organelles such as the endoplasmic reticulum. The complex coregulation of these networks controls how cells respond to dynamic changes in metabolic demand. Recent studies have shown that mitochondrial networks are acutely sensitive to mechanosignalling, but it remains in question whether they respond directly to contractile forces from the cytoskeleton or if their reorganisation occurs downstream of broader metabolic reprogramming. Here we discuss recent work highlighting the complexity in understanding this.