Heat-dependent engagement of a buried mitophagy motif in prohibitin 2

A second LC3-interacting region in prohibitin 2 (PHB2) is temperature-regulated, with purified PHB2 binding ATG8-family proteins only at 313 K and above.

• Why it matters: It tests whether a mitophagy receptor can directly sense a physical stimulus, addressing a gap beyond upstream enzyme control.
• What they did: Replica-scaling simulations and purified-protein binding assays linked helix geometry to LIR accessibility; PHB2-null cardiomyocytes and mice with helix-stabilizing or -destabilizing substitutions were compared.
• The result: Stabilizing substitutions (K253A/R255A) increased mitochondrial recruitment and respiration in PHB2-null cardiomyocytes and, in mice, sustained greater cardiac injury during heat stroke despite matched thermal load.