Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation

TLDR

Mitochondria are dynamic organelles essential for ATP production, apoptosis, and cell‑cycle control, whose morphology shifts between fragmented units and elongated networks in response to regulated signals. Starvation induces mitochondrial elongation by down‑regulating Drp1 through altered phosphorylation at two sites, thereby promoting fusion. Under nutrient depletion, mitochondria elongate and interconnect—an effect amplified by simultaneous nutrient loss—and this tubulation protects them from autophagosomal degradation, preserving energy production and supplying membranes during starvation.

Abstract

Mitochondria are highly dynamic organelles that mediate essential cell functions such as apoptosis and cell-cycle control in addition to their role as efficient ATP generators. Mitochondrial morphology changes are tightly regulated, and their shape can shift between small, fragmented units and larger networks of elongated mitochondria. We demonstrate that mitochondrial elements become significantly elongated and interconnected shortly after nutrient depletion. This mitochondrial morphological shift depends on the type of starvation, with an additive effect observed when multiple nutrients are depleted simultaneously. We further show that starvation-induced mitochondrial elongation is mediated by down-regulation of dynamin-related protein 1 (Drp1) through modulation of two Drp1 phosphorylation sites, leading to unopposed mitochondrial fusion. Finally, we establish that mitochondrial tubulation upon nutrient deprivation protects mitochondria from autophagosomal degradation, which could permit mitochondria to maximize energy production and supply autophagosomal membranes during starvation.