Cover image for Vol. 38 Issue 7

Edited By: Andrew Moore

Online ISSN: 1521-1878



Sometimes called “cellular power plants”, mitochondria are intriguing organelles involved in more processes than the simple production of energy. This special collection of articles takes a look at some of these functions: From the structure of the mitochondrial ribosome and the organisation of mitochondrial DNA to their role in aging. We wish you enjoyable reading!

For further reading, please also take a look at the Encyclopedia of Life SciencesELS-Logo entries under the theme Mitochondria.

Revisiting Kadenbach: Electron flux rate through cytochrome c-oxidase determines the ATP-inhibitory effect and subsequent production of ROS
Sebastian Vogt, Annika Rhiel, Petra Weber, Rabia Ramzan, BioEssays, Volume 38, Issue 6, June 2016, pages 556-567.
DOI: 10.1002/bies.201600043

ATP-binding inhibits Cytochrome c Oxidase, and ROS formation is decreased. This mechanism depends on the quantity of electron transfer to the Heme aa3 of CytOx. In times of stress, ATP-dependent inhibition is switched off and activity of CytOx is exclusively determined by the membrane potential, leading to increased ROS production.

Intracellular evolution of mitochondrial DNA (mtDNA) and the tragedy of the cytoplasmic commons
David Haig, BioEssays, Volume 38, Issue 6, June 2016, pages 549-555.
DOI: 10.1002/bies.201600003

Mitochondria are domesticated prokaryotes that reside in large herds within cells. Female germ cells are the stud farms that stock the herds of the next generation of bodies. Mechanisms of quality control within cells and selection among oogonia and oocytes are the mechanisms of “selective breeding” that maintain herd quality.

The following primary article was published in BioEssays' sister journal Inside the Cell:

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies
Sukhbir S. Dhamrait, Cecilia Maubaret, Ulrik Pedersen-Bjergaard, David J. Brull, Peter Gohlke, John R. Payne, Michael World, Birger Thorsteinsson, Steve E. Humphries and Hugh E. Montgomery, Inside the Cell, Volume 1, Issue 1, pages 70-81.
DOI: 10.1002/icl3.1019

ACE, association studies, endothelial cell, gene expression, genetics, uncoupling protein

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems, which also regulate diverse aspects of whole-body metabolism and mitochondrial function. We demonstrate that ACE expression appears to be regulated by mitochondrial UCPs.

Mitochondrial content is central to nuclear gene expression: Profound implications for human health
Rebecca Muir, Alan Diot and Joanna Poulton, BioEssays, Volume 38, Issue 2, February 2016, pages 150-156.
DOI: 10.1002/bies.201500105

ageing, gene expression, gene regulation, mitochondria, mitochondrial biology, mtDNA, single cell analysis

The amount of energy that mitochondria can generate affects gene expression by influencing protein production at several stages. Cells with the highest mitochondrial content have energy available to activate chromatin, gene transcription, differential alternative splicing of mRNA transcripts, and ribosome biogenesis. This increases protein synthesis and heterogeneity.

Mitochondria and the non-genetic origins of cell-to-cell variability: More is different
Raúl Guantes, Juan Díaz-Colunga and Francisco J. Iborra, BioEssays, Volume 38, Issue 1, January 2016, pages 64-76.
DOI: 10.1002/bies.201500082

alternative splicing, gene expression noise, non-genetic variability, transcription

Gene expression in eukaryotic cells is noisy. Mitochondrial content heterogeneity is a key factor for such variability. Cells with higher mitochondrial mass increase transcription elongation speed, translation, and chromatin activation. This impacts on mRNA and protein accumulation, as well as on alternative splicing, which could affect cell fate.

Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment
Xu Wang, Dongryeol Ryu, Riekelt H. Houtkooper and Johan Auwerx, BioEssays, Volume 37, Issue 10, October 2015, pages 1045-1053.
DOI: 10.1002/bies.201500071

Also watch the Video Abstract.

antibiotiics, chloroplasts, doxycycline, environmental pollution, mitochondria, mitochondrial unfolded protein response, tetracycline

Elevated antibiotic production increases the potential of their environmental release. Many commonly used antibiotics like tetracyclines are acting by inhibiting bacterial protein synthesis as well as translation in mitochondria and chloroplasts, inducing the unfolded protein response in these organelles (UPRmt/UPRcp). To protect our health and the ecosystem, judicious antibiotic usage is required.

The evolution of sex: A new hypothesis based on mitochondrial mutational erosion
Justin C. Havird, Matthew D. Hall and Damian K. Dowling, BioEssays, Volume 37, Issue 9, September 2015, pages 951-958.
DOI: 10.1002/bies.201500057

Also watch the Video Abstract.

cytonuclear, evolutionary genomics, mitochondrial replacement, mito-mutation accumulation, mito-nuclear interactions, organelle, recombination

Widespread sexual reproduction in eukaryotes remains an evolutionary enigma, because asexual reproduction should be favored by selection. We hypothesize that mutation accumulation in the mitochondria, an organelle inextricably linked to eukaryote evolution, would have favored the evolution of sex, because recombination would facilitate nuclear compensatory adaptation to offset mito-induced harm.

Mitochondrial quality control pathways as determinants of metabolic health
Ntsiki M. Held and Riekelt H. Houtkooper, BioEssays, Volume 37, Issue 8, August 2015, pages 867-876.
DOI: 10.1002/bies.201500013

fission, fusion, mitochondrial dynamics, mitochondrial quality control, mitohormesis, mitophagy, ROS

Mitochondrial stress is an important hallmark of metabolic diseases and aging. Various mitochondrial stress response pathways are in place to counter this imposed stress. In this review, we discuss the existing mitochondrial quality control pathways, and focus on the recent insight that these pathways are highly context- and time-dependent.

What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research
Hanne Hoitzing, Iain G. Johnston and Nick S. Jones, BioEssays, Volume 37, Issue 6, June 2015, pages 687–700.
DOI: 10.1002/bies.201400188

hypotheses, mathematical biology, mitochondrial dynamics, mitochondrial networks, non-linearities, ultrastructure

Mitochondria can fuse to form large continuous networks. It is likely that, when hyperfusion occurs, the fused structure is beneficial to the cell. From a mathematical and physical viewpoint, we evaluate existing and novel possible functions of mitochondrial fusion, and we suggest both experiments and modelling approaches to test hypotheses.

Mitochondrial replacement therapy: Cautiously replace the master manipulator
Neil Gemmell and Jonci N. Wolff, BioEssays, Volume 37, Issue 6, June 2015, pages 584-585.
DOI: 10.1002/bies.201500008

mitochondria, commentary

Mitochondria, the powerhouses of our cells, are essential to life. Normal mitochondrial function is achieved through the cooperative interaction of the nuclear and mitochondrial genomes. New IVF approaches intended to circumvent devastating mitochondrial disease look set to change the ancient pattern of mtDNA inheritance and interaction with unknown consequences.

Unique features of DNA replication in mitochondria: A functional and evolutionary perspective
Ian J. Holt and Howard T. Jacobs, BioEssays, Volume 36, Issue 11, November 2014, pages 1024-1031.
DOI: 10.1002/bies.201400052

DNA, double strand breaks, fragile sites, mitochondria, mitochondrial DNA, replication, single strand breaks

Short pieces of RNA serve as precursors to DNA replication in many systems, but the long RNAs hybridized to replicating DNA in mitochondria are unusual if not unique. Here we discuss the virtues of threading RNA transcripts (aka bootlaces) onto the lagging-strand template, rather than the conventional approach of synthesizing DNA concurrently on both strands.

Of early animals, anaerobic mitochondria, and a modern sponge
Marek Mentel, Mayo Röttger, Sally Leys, Aloysius G. M. Tielens and William F. Martin, BioEssays, Volume 36, Issue 10, October 2014, pages 924-932.
DOI: 10.1002/bies.201400060

anaerobiosis, eukaryotes, geochemistry, hypoxia, mitochondria, Neoproterozoic ocean chemistry, rhodoquinone

Some mitochondria respire oxygen and some mitochondria make ATP without oxygen. Such anaerobic mitochondria can be found among various eukaryotes, but they have been best studied among the animals (invertebrates). Many scientists are interested in better understanding the role of oxygen in animal evolution, where anaerobic mitochondria figure prominently.

How the mitochondrion was shaped by radical differences in substrates
Dave Speijer, BioEssays, Volume 36, Issue 7, July 2014, pages 634-643.
DOI: 10.1002/bies.201400033

beta-oxidation, carnitine shuttle, FADH2/NADH ration, mitochondria, oxygen radicals, peroxisomes, UCPs

As alpha-proteobacteria and archaea integrated to form eukaryotes, the mitochondrion-to-be produced increased internal reactive oxygen species (ROS), especially during fatty acid oxidation. Resulting selection pressures favoured evolution of eukaryotic ‘innovations’: reducing ROS formation (peroxisomes, uncoupling proteins (UCPs), respiratory chain supercomplex formation); lessening ROS effects (mitochondrial genome reduction, antioxidants, mitophagy); or both (carnitine shuttles).

Mitochondrial fission-fusion as an emerging key regulator of cell proliferation and differentiation
Kasturi Mitra, BioEssays, Volume 35, Issue 11, November 2013, pages 955-964.
DOI: 10.1002/bies.201300011

cell cycle, cell differentiation, cell proliferation, mitochondrial fission, mitochondrial fusion

The decision to remain in a proliferative state or to exit toward differentiation, quiescence, or senescence is key for cells in the developmental journey. I propose that mitochondrial morphology, controlled by mitochondrial fission-fusion proteins, is a crucial factor for guiding such cellular decisions, aberrations in which may lead to developmental anomalies.

Quality control of mitochondria during aging: Is there a good and a bad side of mitochondrial dynamics?
Marc Thilo Figge, Heinz D. Osiewacz and Andreas S. Reichert, BioEssays, Volume 35, Issue 4, April 2013, pages 314-322.
DOI: 10.1002/bies.201200125

aging, mitochondrial biology, mitochondrial dynamics, systems biology

Mitochondria are essential eukaryotic organelles that represent a cellular “achilles heel”. Different pathways are active keeping mitochondria functional over time, including cycles of fusion and fission. We hypothesize that during aging mitochondrial dynamics may not only be beneficial but represents a double-edged sword with a good and a bad side.

Tuning a ménage à trois: Co-evolution and co-adaptation of nuclear and organellar genomes in plants
Stephan Greiner and Ralph Bock, BioEssays, Volume 35, Issue 4, April 2013, pages 354-365.
DOI: 10.1002/bies.201200137

chloroplast capture, co-evolution, cytoplasmic incompatibility, cytoplasmic male sterility, hybridization barrier, plastome-genome incompatibility, speciation

Increasing evidence suggests that organellar (plastid and mitochondrial) genomes contribute significantly to environmental adaptation. As organellar genomes co-evolve with the nuclear genome, exchange of organelles between species or populations can result in genome conflicts (cytoplasmic incompatibilities). These incompatibilities can contribute to the establishment of hybridization barriers, ultimately leading to speciation.

Mitochondria, maternal inheritance, and asymmetric fitness: Why males die younger
Jonci N. Wolff and Neil J. Gemmell, BioEssays, Volume 35, Issue 2, February 2013, pages 93-99.
DOI: 10.1002/bies.201200141

asymmetry, Drosophila, evolution, mitochondria, mtDNA, oxphos, selection

The maternal inheritance of mtDNA results in a selection asymmetry; natural selection cannot act on mutations that affect only males. This asymmetry imposes a male-specific mutation load previously implicated in male disease and infertility. New work suggests this asymmetry underpins the strong sexual dimorphism in aging observed across taxa.