Cubic membrane formation supports cell survival of amoeba Chaos under starvation-induced stress

Cubic membranes (CM) are highly organized membrane structures found in biological systems. They are mathematically well defined and reveal a three-dimensional nano-periodic structure with cubic symmetry. These membrane arrangements are frequently induced in cells under stress, disease conditions, or upon viral infection. In this study, we investigated CM formation in the mitochondria of amoeba Chaos carolinense and observed a striking correlation between the organism's ability to generate CM and the cell survival under starvation. Since starvation also induces autophagy, rapamycin was used to pharmacologically induce autophagy, and interestingly, CM formation was observed in parallel. Conversely, inhibition of autophagy reverted the cubic mitochondrial inner membrane morphology to tubular structure. In starved Chaos cells, mitochondria and autophagosomes did not co-localize and ATP production was sustained. CM transition in the mitochondria during starvation or upon induction of autophagy might prevent their sequestration by autophagosomes, thus slowing their rate of degradation. Such sustained mitochondrial activity may allow amoeba Chaos cells to survive for a longer period upon starvation.