Dataset Information

Mitochondrial pathway of apoptosis is ancestral in metazoans.

ABSTRACT: The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome c, which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. Here we show that apoptosis in a lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and that cytochrome c triggers caspase activation in cytosolic extracts from these animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate MOMP. These results suggest that the mitochondrial pathway of apoptosis in animals predates the emergence of the vertebrates but was lost in some lineages (e.g., nematodes). In further support of this hypothesis, we surveyed the ability of cytochrome c to trigger caspase activation in cytosolic extracts from a variety of organisms and found this effect in cytosolic extracts from invertebrate deuterostomes (phylum Echinodermata).

SUBMITTER: Bender CE

PROVIDER: S-EPMC3324028 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mitochondrial pathway of apoptosis is ancestral in metazoans.

Bender Cheryl E CE Fitzgerald Patrick P Tait Stephen W G SW Llambi Fabien F McStay Gavin P GP Tupper Douglas O DO Pellettieri Jason J Sánchez Alvarado Alejandro A Salvesen Guy S GS Green Douglas R DR

Proceedings of the National Academy of Sciences of the United States of America 20120313 13

The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome c, which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. ...[more]

PMID: 22416118

Similar Datasets

Project description:BackgroundBasal metabolic rate (BMR) has a very strong body-mass (M) dependence in an individual animal group, and BMR per unit mass (msBMR) converges on a markedly narrow range even across major taxonomic groups. However, it is here a basic question in metazoan biology how much BMR per unit mitochondrion (mtBMR) changes, and then whether mtBMR can be related to the original molecular mechanism of action of mt-encoded membrane proteins (MMPs) playing a central role in cellular energy production.Methodology/principal findingsAnalyzing variations of amino-acid compositions of MMPs across 13 metazoan animal groups, incorporating 2022 sequences, we found a strong inverse correlation between Ser/Thr composition (STC) and hydrophobicity (HYD). A majority of animal groups showed an evolutionary pathway of a gradual increase in HYD and decrease in STC, whereas only the deuterostome lineage revealed a rapid decrease in HYD and increase in STC. The strongest correlations appeared in 5 large subunits (ND4, ND5, ND2, CO1, and CO3) undergoing dynamic conformational changes for the proton-pumping function. The pathway of the majority groups is well understood as reflecting natural selection to reduce mtBMR, since simply raising HYD in MMPs (surrounded by the lipid bilayer) weakens their mobility and strengthens their stability. On the other hand, the marked decrease in HYD of the deuterostome elevates mtBMR, but is accompanied with their instability heightening a turnover rate of mitochondria and then cells. Interestingly, cooperative networks of interhelical hydrogen-bonds between motifs involving Ser and Thr residues can enhance MMP stability.Conclusion/significanceThis stability enhancement lowers turnover rates of mitochondria/cells and may prolong even longevity, and was indeed founded by strong positive correlations of STC with both mtBMR and longevity. The lowest HYD and highest STC in Aves and Mammals are congruent with their very high mtBMR and long longevity.

Dataset Information

Mitochondrial pathway of apoptosis is ancestral in metazoans.

Publications

Mitochondrial pathway of apoptosis is ancestral in metazoans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets