Research Perspective Volume 2, Issue 12 pp 1023—1029

Zfra is a small wizard in the mitochondrial apoptosis

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Figure 1. Zfra in the mitochondrial pathway of apoptosis. UV light induces Zfra phosphorylation (pZfra) at Ser8 and translocation to the nuclei (Route 1). Zfra rapidly undergoes de-phosphorylation and degradation in the nuclei [29]. However, in response to stimuli for the mitochondrial pathway of apoptosis, Zfra becomes Ser8-phosphorylated and relocates, along with p53 and WOX1, to the mitochondria. Ectopic Zfra significantly downregulates Bcl-2 and Bcl-xL (Route 2), blocks cytochrome c release by interacting with voltage-dependent anion channel (VDAC) (Route 3), and yet induces dissipation of mitochondrial membrane potential [29]. Alternatively, Zfra probably interacts with cytochrome c to block its release from the mitochondria. Zfra binds and blocks the apoptotic function of WOX1 (Route 4). Overexpressed WOX1 induces cytochrome c release (Route 5) [29]. By the same token, Zfra blocks apoptotic function of p53 in the mitochondria.