UC Santa Barbara

Cell death is fundamental in animal development, tissue homeostasis, and disease. Approximately 50 billion cells die by apoptosis every day in an adult human. During apoptosis, mitochondrial permeabilization results in the activation of caspase proteases. Caspases cleave hundreds of protein targets killing the cell and fragmenting it into apoptotic bodies for immune clearance. Cell death research has long suggested that once mitochondrial dysfunction and caspase activation are observed, death is inevitable. However, a growing body of research challenges this long-standing assumption. A variety of normal and cancer cell types can survive transient activation of apoptosis in a process termed anastasis.

I study anastasis using human cancer cell lines, representing some of the most prevalent cancer types, as a model. I first document major phenotypic changes following transient treatment of the apoptosis inducer staurosporine (STS). I observed cancer cells recovering from STS induced mitochondrial collapse and damage. From these observations, I discovered that anastatic cancer cells survive with low mitochondrial membrane potential (ΔΨm) and that low ΔΨm correlated with nuclear health. This dissertation provides a cell biological description of anastasis in cervical cancer HeLa cells and reveals a previously unknown connection between anastasis and metabolic reprogramming.