Prohibitin-2

Prohibitin-2 (PHB2) is a multifunctional protein with roles spanning mitochondria, nucleus, and plasma membrane (UniProt: Q99623). In mitochondria, it assembles with PHB to form ring complexes within the inner membrane, functioning as a chaperone that stabilizes respiratory enzymes, maintains mitochondrial integrity, and regulates cytochrome c oxidase assembly and mitochondrial respiration. PHB2 also serves as a mitophagy receptor targeting mitochondria for autophagic degradation and participates in mitochondrial antiviral immunity. In the nucleus, it acts as a transcriptional coregulator of hormone receptors, while at the plasma membrane it mediates cell signaling and B cell activation.

PHB2 is implicated in Alzheimer's disease pathology. In post-mortem AD brain tissue compared to age-matched controls, PHB2 is significantly upregulated with a mean log2 fold-change of 1.58 (Chaparral AD proteomics). This upregulation was detected across the TMT-labeled subcellular fractions in a DDA proteomics experiment. The increased abundance of this mitochondrial chaperone and autophagy regulator may reflect compensatory cellular responses to mitochondrial dysfunction or increased protein quality-control demands characteristic of AD neurodegeneration.