What is the relative contribution of connexin-43 gap junctions vs tunneling nanotubes to mitochondrial transfer?

The debate revealed conflicting evidence about whether connexin-43 mediates mitochondrial transfer through gap junctions or tunneling nanotubes. This mechanistic uncertainty undermines therapeutic targeting strategies and requires direct experimental disambiguation.

Source: Debate session sess_SDA-2026-04-01-gap-20260401231108 (Analysis: SDA-2026-04-01-gap-20260401231108)

Resolved when direct live-cell or ultrastructural experiments distinguish connexin-43 gap junction transfer from tunneling nanotube-mediated mitochondrial transfer using orthogonal perturbations for each route. Criteria require quantitative mitochondrial transfer rates, recipient-cell rescue or harm readouts, imaging evidence of route usage, replication in neuron-glia or relevant CNS cell models, and KG edges assigning mechanism-specific evidence to connexin-43 and tunneling nanotube pathways.