Mitochondrial pull-outs are a distinct type of dynamic tubulation events regulated by mitochondrial activity

Abstract

Mitochondrial networks undergo continuous remodeling through fusion and fission, processes that are essential for maintaining energy production and cellular homeostasis. Rapid elongation of the tip of mitochondrial tubules, a process termed dynamic tubulation, also participates in mitochondrial network formation. However, these mechanisms alone cannot fully account for the formation of highly interconnected mitochondrial networks that are required for rapid distribution of mitochondria material. Here, we identify a distinct type of dynamic tubulation, mitochondrial pull-outs characterized by the lateral extrusion from pre-existing mitochondrial tubules, as metabolically regulated determinants of mitochondrial network formation. Pull-outs are distinct from the tip elongation form of dynamic tubulation as they are modulated by the mitochondrial dynamins MFN1 and DRP1 and are stimulated by conditions favoring oxidative phosphorylation. Pull-outs also depend on mitochondrial actin polymerization and are required to increase mitochondrial connectivity and respiratory activity. Together, these findings establish mitochondrial pull-out as a metabolically sensitive mechanism that promotes mitochondrial network connectivity and links organelle architecture to cellular energy demands.