T cell mitochondrial network and uptake machinery

The T cell mitochondrial network and uptake machinery is a complex functional system responsible for the organization of mitochondria and the acquisition of these organelles from the extracellular environment to regulate T cell metabolic fitness and effector function. This machinery includes proteins governing mitochondrial dynamics, such as OPA1 and Mitofusins (Mfn1/2) for fusion and DRP1 for fission, as well as structures facilitating intercellular mitochondrial transfer, such as tunneling nanotubes (TNTs) and extracellular vesicles (EVs) [1, 4]. In the tumor microenvironment, this system is a critical mediator of immune evasion, as cancer cells can "hijack" mitochondria from infiltrating T cells through TNTs, leading to T cell metabolic depletion and exhaustion [1, 7]. Conversely, in inflammatory conditions like asthma, regulatory cells may transfer mitochondria to T cells to modulate their pro-inflammatory signaling [4, 6]. Therapeutic strategies targeting this machinery aim to either block the parasitic transfer of mitochondria to cancer cells or enhance the mitochondrial fitness of T cells in adoptive cell therapies, such as CAR-T, to improve their persistence and anti-tumor efficacy [1, 2].

Other names

Intercellular mitochondrial transfer (IMT) machineryMitochondrial hijacking systemT cell mitochondrial dynamics and acquisition complexTNT-mediated mitochondrial uptake machineryMitochondrial fitness and fusion-fission network

Inhibition of mitochondrial fission via DRP1 blockade; disruption of tunneling nanotube (TNT) formation through farnesyltransferase inhibition; modulation of mitochondrial fusion and network integrity via OPA1/Mitofusin activation; inhibition of actin polymerization to prevent organelle transfer.