Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms

Abstract

Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis: ( a) Differentiation and embryogenesis rely on mitochondrial function; ( b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; ( c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders. Expected final online publication date for the Annual Review of Genetics, Volume 54 is November 23, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Diverse Functions of Tim50, a Component of the Mitochondrial Inner Membrane Protein Translocase

“…Mitochondria are evolved from the endosymbiont proteobacteria [1]. Thus, like its ancestor, mitochondria are surrounded by double membranes.…”

Exploring patterns of cytonuclear incompatibility in Pelargonium section Ciconium

“…For the chloroplast, the timing of endosymbiosis is tentatively put at 2.1 Gya and it took ~200 MY before the first branching of extant lineages occurred (Sánchez-Baracaldo et al 2017). the scientific consensus is that the inclusion of these organelles made more complex life possible (Medini et al 2020). The stable inclusion of the mitochondria and chloroplasts was further achieved by the transfer of many organellar genes , not directly involved in photosynthesis or respiration (the oxidative phosphorylation pathway), to the nucleus (Martin et al 2002, Ku et al 2015.…”

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

“…(2) ALR also protects renal tubular epithelial cells from IRI by promoting PINK1/Parkin-mediated mitophagy [52]. (3) The mitochondrial metal transporters mitoferrin1 (Mfm1) and mitoferrin2 (Mfm2) are required for liver regeneration. Loss of both mitoferrins in hepatocytes dramatically reduced regeneration in adult mouse liver [53].…”

“…The cytoplasm of eukaryotic cells, in contrast to these organelles, exerts anaerobic glycolysis, such as in ancient times. Mitochondria have been (and are) fundamental for the emergence of metazoans [3]. The perpetual work of these cellular organelles over billions of years under changing environmental conditions is of great fascination.…”