The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.

Migrasomes, released by migrating cells, belong to the heterogeneous world of extracellular vesicles (EVs). However, they can be distinguished from all other members of EVs by their size, biorigin and protein cargo. As far as we know, they can play important roles in various communication processes, by mediating the release of signals, such as mRNAs, proteins or damaged mitochondria. To extend and better understand the functional roles and importance of migrasomes, it is first essential to well understand the basic molecular mechanisms behind their formation and function. Herein, we endeavor to provide a brief and up-to-date description of migrasome biogenesis, release, characterization, biological properties and functional activities in cell-to-cell communication, and we will discuss and propose putative new functions for these vesicles.

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