Effect of mitochondrial circulation on mitochondrial age density distribution

Abstract

Recent publications report that although mitochondria population in an axon can be quickly replaced by combination of retrograde and anterograde axonal transport (often within less than 24 h), the axon contains much older mitochondria. This suggests that not all mitochondria that reach the soma are degraded, some of them participate in recirculation. To explain this we developed a model that simulates that a portion of mitochondria that return to the soma are redirected back to the axon rather than being destroyed in somatic lysosomes. Utilizing the developed model, we studied how the percentage of returning mitochondria affects the mean age and age density distributions of mitochondria at different distances from the soma. We also investigated whether turning off the mitochondria anchoring switch can reduce the mean age of mitochondria. For this purpose, we studied the effect of reducing the value of a parameter that characterizes the probability of mitochondria transition to the stationary (anchored) state. The reduction of the mean age of mitochondria observed when the chance of mitochondria to get anchored is reduced suggests that some injured neurons may be saved if the percentage of stationary mitochondria is decreased. Replacement of possibly damaged stationary mitochondria with newly synthesized ones may restore energy supply in an injured axon. We also performed a sensitivity study of the mean age of stationary mitochondria to the parameter that determines what portion of mitochondria re-enter the axon and the parameter that determines the probability of mitochondria transition to the stationary state.

Mitochondrial Transport in Symmetric and Asymmetric Axons with Multiple Branching Junctions: A Computational Study

“…Kuznetsov and Kuznetsov (2022a, 2022b, 2023) developed an alternative model of mitochondria transport in an axon that is based on simulating mitochondria transport and accumulation in various energy demand sites. The motivation was to apply powerful methods developed for compartmental systems (Metzler et al 2018; Metzler and Sierra 2018) to determine mean age and age density distributions of mitochondria in demand sites located at different distances from the soma.…”