The role of Agc1 in the interplay between mitochondrial dynamics and cellular metabolism

Mitochondria are pivotal for a variety of cellular processes, from energy production to regulation of programmed cell death. Cellular metabolism and mitochondrial dynamics are without any doubt intertwined, however it remains uncertain the causality relationship existing between them. This work analyzes the ability of mitochondria to perceive metabolic cues through Agc1 as intermediary. We identified that Agc1-KO C2C12 cells were unable to adapt to starvation, as demonstrated by the reduced Opa1 oligomerization level and reduced mitochondria length increase if compared to control. We also identified that, upon starvation, Agc1 switches from dimeric to monomeric form. Moreover, we identified that Agc1 not only interacts with Opa1, a well-known fusion protein involved also in the cristae structure maintenance, but also Agc1 forms a complex with Opa1. All these findings, in addition with the ability of Agc1 activity to be regulated by cytoplasmatic Calcium concentration, validate Agc1 as intermediary in the transduction of metabolic cues from cell to mitochondrion, although the precise mechanism has yet to be discovered.