Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.

基因调控的细胞死亡（RCD）发生在生活的所有领域。在真核生物中，线粒体和某些形式的RCD（特别是细胞凋亡）的进化起源被认为是一致的，这表明线粒体在细胞自杀中起着核心的一般作用。我们在67种原生生物的数据集中测试了这种线粒体中心性假设，提出了5类线粒体表型，包括功能性线粒体，代谢多样化的线粒体，功能降低的线粒体（线粒体相关细胞器或MRO），甚至完全不存在线粒体。我们调查了与各种形式的RCD相关的基因的分布。在我们的67个单细胞分类群中，没有发现所描述的哺乳动物坏死调节因子的同源物。流苏单核菌与典型的线粒体原生生物相比，它显示出凋亡基因集的异质减少。值得注意的是，尽管沙门氏菌，仍然可以确定凋亡相关基因。这些具有MRO和沙门氏菌携带非减少的自噬细胞死亡基因集。而且，与自由生活的原生生物相比，瞬时多细胞原生生物分类单元似乎富含凋亡和自噬相关基因。这项分析表明，与动物凋亡相关的基因和线粒体的存在是原生动物中RCD的重要但非必需的生物学组成部分。更普遍地，我们的结果支持选择RCD（包括凋亡和自噬）作为与多细胞性相关的发育机制的假设。