Mitochondrial involvement in cell death of non-mammalian eukaryotes

Abstract

Although mitochondria are essential organelles for long-term survival of eukaryotic cells, recent discoveries in biochemistry and genetics have advanced our understanding of the requirements for mitochondria in cell death. Much of what we understand about cell death is based on the identification of conserved cell death genes in Drosophila melanogaster and Caenorhabditis elegans. However, the role of mitochondria in cell death in these models has been much less clear. Considering the active role that mitochondria play in apoptosis in mammalian cells, the mitochondrial contribution to cell death in non-mammalian systems has been an area of active investigation. In this article, we review the current research on this topic in three non-mammalian models, C. elegans, Drosophila and Saccharomyces cerevisiae. In addition, we discuss how non-mammalian models have provided important insight into the mechanisms of human disease as they relate to the mitochondrial pathway of cell death. The unique perspective derived from each of these model systems provides a more complete understanding of mitochondria in programmed cell death.

Fipronil induces apoptosis through caspase-dependent mitochondrial pathways in Drosophila S2 cells

“…Electron microscopy analysis has shown that spermatid development is grossly disrupted in animals that carry mutations in Cyt c [38]. In contrast, in several other cells, Cyt c is not the core protein for apoptosis, such as Drosophila SL2 cells or BG2 cells [37,39]. Furthermore, the addition of Cyt c to Drosophila cell extracts results in only a modest (an approximate two-fold) caspase activation [40].…”

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

“…51 However, mitochondrial involvement in apoptosis in Drosophila remains uncertain. 52,53 Particularly, the cytochrome c involvement in the apoptosome activation is highly debatable. 28 Instead of being a direct 'activator', mitochondria are considered as the docking sites to receive death signals and release proapoptotic molecules.…”

Detecting apoptosis in Drosophila tissues and cells

“…Mitochondrial fission and fusion are altered in apoptotic cells, and changes in mitochondrial dynamics can influence the apoptotic sensitivity of cells (reviewed in [20]). Mitochondrial morphology can be assessed with a ubiquitously expressed mitochondrial localized GFP, SpSqEYFP-mito (mito-GFP) [21], in which EYFP is fused to a mitochondrial targeting sequence from Complex VIII of cytochrome C oxidase (Fig.…”