Figure 12. Schematic model depicting the role of Rab5-Alsin-mitochondria during oxidative stress.

In the normal condition, mitochondria (Mito, red) are elongated and tubular (left). Rab5 (green) are localized on early endosomes (EE) to assemble the Rab5 machinery for endosomal maturation and membrane trafficking. At steady state, some EE make transient contacts with mitochondria. During oxidative stress (e.g. laser- or chemically-induced), mitochondria undergo MOMP and a dramatic morphological transformation into rounded and swollen structures (right). The release of the apoptotic factor, cytochrome c, from mitochondria into the cytosol is associated with a re-localization event of Rab5 from EE to mitochondria via a cytosolic intermediate, accompanied by an increase in EE-mitochondria MCS. The recruitment and activation of Rab5 on mitochondria depend on the Rab5 GEF Alsin (blue), which leads to a selective recruitment of Rabenosyn-5 (light green). This signaling cascade on mitochondria is a reversible process that regulates the apoptotic program (e.g. cytochrome c release and caspase activation) and thus, promotes overall cell survival.