PITRM1 (F2Y2T) Rabbit Monoclonal Antibody #89774

Pitrilysin metalloproteinase 1 (PITRM1 or PreP) is a mitochondria-enriched presequence peptidase that processes the mitochondrial targeting sequence (MTS) of proteins imported across the inner mitochondrial membrane (1). Mitochondria normally function to regulate many cellular processes, such as energy production and apoptosis, and its dysfunction may contribute indirectly or directly to human neurodegenerative diseases like Alzheimer’s disease (AD) (2) and Parkinson’s disease (PD) (3). Interestingly, β-amyloid peptide (Aβ), the pathological hallmark of AD, accumulates in mitochondria and inhibits Cym1, the PITRM1 yeast ortholog, leading to impaired MTS processing and accumulation of unprocessed mitochondrial proteins, suggesting an indirect role of Aβ and mitochondrial dysfunction via PITRM1 (4). In addition to biochemical association of PITRM1 with Aβ-dependent mitochondrial dysfunction, human genetics suggest a more direct link as PITRM1 genetic variants have been associated with AD (5,6). The specific mechanism is currently poorly understood but may involve impairment of PITRM1-dependent degradation of Aβ, directly resulting in pathological accumulation of Aβ in mitochondria (6).