FIGURE 2.

The current model of cellular and molecular mechanisms behind mitochondrial transfer. (A) EVs-mediated MT is regulated through the CD38/cADPR signaling, inducing calcium release from the endoplasmic reticulum. The CD38 activity can be post-translationally modulated through O-GlcNAcylation and phosphorylation, and its expression is induced in a Sig1R-dependent manner. (B) Connexins’ protein expression, assembly, and stabilization are precisely controlled through different kinases, such as PKA, PKC, MAPK, CK1, and CAMKII. Gap junctions-mediated MT is predicted to facilitate the donation of low-weight molecules comprising energetic nucleotides and mitochondrial respiratory complexes. (C) The formation of TNTs relies on the molecular interaction between MIRO1 and accessory motor enzymes like dynein, kinesins, and myosins. TNT-mediated MT entails donating complete mitochondrial units, whose subcellular fate is still the subject of discussion. The complexity of the exocytic pathway is not fully depicted. Question marks denote mechanisms not currently described. MT, mitochondrial transfer; PKA, protein kinase A; PKC, protein kinase C; MAPK, mitogen-activated protein kinase (MAPK); CK1, casein kinase 1; and CAMKII, Ca²⁺/calmodulin-dependent kinase II. The figure was created in BioRender.com.