1. ¹Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD, USA
2. ²Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
3. ³Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA
4. ⁴Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
5. ⁵Department of Endocrinology, Yale University, New Haven, CT, USA
6. ⁶Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
7. ⁷Department of Pharmacology, Yale University, New Haven, CT, USA

Correspondence: Dr JM Hardwick, Department of Molecular Microbiology and Immunology, Rm E5140 BSPH, Johns Hopkins, 615 N. Wolfe St. Baltimore, MD 21205, USA. E-mail: hardwick@jhu.edu

Abstract

At least in mammals, we have some understanding of how caspases facilitate mitochondria-mediated cell death, but the biochemical mechanisms by which other factors promote or inhibit programmed cell death are not understood. Moreover, most of these factors are only studied after treating cells with a death stimulus. A growing body of new evidence suggests that cell death regulators also have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins and pro-death Bcl-2 family proteins appear to have normal cellular functions that promote cell survival. Here, we review some of the supporting evidence and stretch beyond the evidence to seek an understanding of the remaining questions.