Nonequilibrium temperature fluctuations as modulators of mitochondrial elastocapillary stability.

Recent studies have suggested that under high or near-maximal mitochondrial respiratory activity, ion-translocating proteins within the inner mitochondrial membrane may generate transient nonequilibrium temperature fluctuations in the adjacent mitochondrial matrix and intermembrane space. Such nonequilibrium temperature fluctuations may, in principle, influence mitochondrial mechanics and morphology. Building on elastocapillary models of mitochondrial dynamics, we investigate whether these nonequilibrium temperature fluctuations can modulate the stability of mitochondrial tubules through temperature-dependent changes in effective membrane tension and elasticity. Our numerical analysis predicts that this effect is strongly threshold-dependent: in deeply unstable states, thermal modulation remains insufficient to restore stability, whereas closer to the threshold, temperature-dependent reduction of effective membrane tension can overcome temperature-dependent elastic softening, thereby increasing the elastocapillary number, suppressing unstable modes, and shifting mitochondria toward mechanically more stable tubular states. In other words, when mitochondria begin shifting toward fission-promoting states, elevated respiratory activity, which increases the magnitude and cumulative temporal occupancy of transient thermal perturbations, tends to shift the system back toward mechanical stability. However, when mitochondria are already far within the mechanically unstable regime, transient thermal activity is no longer sufficient to restore stability. This stabilizing regime is qualitatively consistent with experimental observations linking elevated oxidative phosphorylation to mitochondrial elongation, fusion, or hyperfusion rather than fragmentation.