Regulation of mitochondrial apoptosis by Pin1 in cancer and neurodegeneration

• Pin1 is a key regulator of apoptotic events in response to various stresses.
• Pin1 is directly involved in activating the mitochondrial apoptosis cascade.
• Based on the cellular context, Pin1 can exert either pro-anti-apoptotic activities.
• Pin1 intercepts cellular metabolic pathways.
• The role of Pin1 in apoptosis has an impact in cancer and neurodegenerative diseases.

Mitochondria are sensitive and efficient organelles that regulate essential biological processes including: energy metabolism, decoding and transduction of intracellular signals, and balance between cell death and survival. Of note, dysfunctions in mitochondrial physiology are a general hallmark of cancer cells, leading to transformation-related features such as altered cellular metabolism, survival under stress conditions and reduced apoptotic response to chemotherapy. Mitochondrial apoptosis is a finely regulated process that derives from activation of multiple signaling networks. A crucial biochemical requirement for transducing pro-apoptotic stimuli is represented by kinase-dependent phosphorylation cascades. In this context a pivotal role is played by the prolyl-isomerase Pin1, which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates. In this review we will discuss the impact of Pin1 in regulating various aspects of apoptosis in different biological contexts with particular emphasis on cancer and neurodegenerative diseases.