Mitochondrial cristae are connected to the inner boundary membrane via crista junctions which are implicated in the regulation of oxidative phosphorylation, apoptosis, and import of lipids and ...proteins. The MICOS complex determines formation of crista junctions. We performed complexome profiling and identified Mic13, also termed Qil1, as a subunit of the MICOS complex. We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex. Using the CRISPR/Cas method we generated the first cell line deleted for MIC13. These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions. MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex suggesting that the latter is not sufficient for crista junction formation. MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration. In summary, we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.
Mitochondria are vital cellular organelles involved in a plethora of cellular processes such as energy conversion, calcium homeostasis, heme biogenesis, regulation of apoptosis and ROS reactive ...oxygen species (ROS) production. Although they are frequently depicted as static bean-shaped structures, our view has markedly changed over the past few decades as many studies have revealed a remarkable dynamicity of mitochondrial shapes and sizes both at the cellular and intra-mitochondrial levels. Aberrant changes in mitochondrial dynamics and cristae structure are associated with ageing and numerous human diseases (e.g., cancer, diabetes, various neurodegenerative diseases, types of neuro- and myopathies). Another unique feature of mitochondria is that they harbor their own genome, the mitochondrial DNA (mtDNA). MtDNA exists in several hundreds to thousands of copies per cell and is arranged and packaged in the mitochondrial matrix in structures termed mt-nucleoids. Many human diseases are mechanistically linked to mitochondrial dysfunction and alteration of the number and/or the integrity of mtDNA. In particular, several recent studies identified remarkable and partly unexpected links between mitochondrial structure, fusion and fission dynamics, and mtDNA. In this review, we will provide an overview about these recent insights and aim to clarify how mitochondrial dynamics, cristae ultrastructure and mtDNA structure influence each other and determine mitochondrial functions.
The mitochondrial membrane potential (ΔΨm) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), ...is considered to carry a uniform ΔΨm. However, sequestration of OXPHOS components in cristae membranes necessitates a re‐examination of the equipotential representation of the IMM. We developed an approach to monitor ΔΨm at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨm, corresponding to cristae and IBM. ΔΨm was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨm heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS‐complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨm. Lastly, we determined that different cristae within the individual mitochondrion can have disparate membrane potentials and that interventions causing acute depolarization may affect some cristae while sparing others. Altogether, our data support a new model in which cristae within the same mitochondrion behave as independent bioenergetic units, preventing the failure of specific cristae from spreading dysfunction to the rest.
Synopsis
Mitochondrial membrane potential (ΔΨm) is the main driving force for ATP synthesis at the folds of the inner mitochondrial membrane, the cristae. Measurement of ΔΨm in individual cristae reveals that crista junctions provide electrical insulation and sustain polarization of individual mitochondrial cristae within a single mitochondrion even when neighbouring cristae are damaged.
Cristae have higher ΔΨ compared to their adjoining inner mitochondrial membranes.
Cristae are electrically insulated, allowing individual cristae within any given mitochondrion to have different membrane potentials.
Cristae can remain polarized despite depolarization of neighbouring ones.
Disruption of crista junctions impairs the electrical insulation of cristae, equilibrating their ΔΨ with those of inner mitochondrial membranes.
Crista junctions provide electrical insulation and sustain polarization of individual mitochondrial cristae within a single mitochondrion even when neighbouring cristae are damaged.
Animal contests govern access to key resources and are a fundamental determinant of fitness within populations. Little is known about the mechanisms generating individual variation in strategic ...contest behavior or what this variation means for population level processes. Cognition governs the expression of behaviors during contests, most notably by linking experience gained with decision making, but its role in driving the evolutionary ecological dynamics of contests is only beginning to emerge. We review the kinds of cognitive mechanisms that underlie contest behavior, emphasize the importance of feedback loops and socio-ecological context, and suggest that contest behavior provides an ideal focus for integrative studies of phenotypic variation.
Animal contests are important determinants of fitness.
Cognition mediates contest behaviors, but its role is underappreciated.
New theory, technologies, and methodologies facilitate the study of contest cognition.
We develop a framework linking cognition, contests, fitness, and ecology.
Mitochondria are double membrane-bound organelles in eukaryotic cells essential to a variety of cellular functions including energy conversion and ATP production, iron-sulfur biogenesis, lipid and ...amino acid metabolism, and regulating apoptosis and stress responses. Mitochondrial dysfunction is mechanistically linked to several neurodegenerative diseases, cancer, and ageing. Excessive and dysfunctional/damaged mitochondria are degraded by selective autophagic pathways known as mitophagy. Both budding yeast and mammals use the well-conserved machinery of core autophagy-related genes (
) to execute and regulate mitophagy. In mammalian cells, the PINK1-PARKIN mitophagy pathway is a well-studied pathway that senses dysfunctional mitochondria and marks them for degradation in the lysosome. PINK1-PARKIN mediated mitophagy relies on ubiquitin-binding mitophagy adaptors that are non-ATG proteins. Loss-of-function mutations in
and
are linked to Parkinson´s disease (PD) in humans, and defective mitophagy is proposed to be a main pathomechanism. Despite the common view that yeast cells lack PINK1- and PARKIN-homologs and that mitophagy in yeast is solely regulated by receptor-mediated mitophagy, some studies suggest that a ubiquitination-dependent mitophagy pathway also exists. Here, we will discuss shared mechanisms between mammals and yeast, how mitophagy in the latter is regulated in a ubiquitin-dependent and -independent manner, and why these pathways are essential for yeast cell survival and fitness under various physiological stress conditions.
Macromolecular complexes are essential players in numerous biological processes. They are often large, dynamic, and rather labile; approaches to study them are scarce. Covering masses up to ∼30 MDa, ...we separated the native complexome of rat heart mitochondria by blue-native and large-pore blue-native gel electrophoresis to analyze its constituents by mass spectrometry. Similarities in migration patterns allowed hierarchical clustering into interaction profiles representing a comprehensive analysis of soluble and membrane-bound complexes of an entire organelle. The power of this bottom-up approach was validated with well-characterized mitochondrial multiprotein complexes. TMEM126B was found to comigrate with known assembly factors of mitochondrial complex I, namely CIA30, Ecsit, and Acad9. We propose terming this complex mitochondrial complex I assembly (MCIA) complex. Furthermore, we demonstrate that TMEM126B is required for assembly of complex I. In summary, complexome profiling is a powerful and unbiased technique allowing the identification of previously overlooked components of large multiprotein complexes.
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► Multiprotein complexes up to a mass of 30 MDa are analyzed by proteomic profiling ► The power of complexome profiling is shown for mitochondrial multiprotein complexes ► TMEM126B is essential for the assembly of mitochondrial complex I ► TMEM126B is a subunit of the mitochondrial complex I assembly (MCIA) complex
Mitochondria are double-membrane enclosed eukaryotic organelles with a central role in numerous cellular functions. The ultrastructure of mitochondria varies considerably between tissues, organisms, ...and the physiological state of cells. Alterations and remodeling of inner membrane structures are evident in numerous human disorders and during apoptosis. The inner membrane is composed of two subcompartments, the cristae membrane and the inner boundary membrane. Recent advances in electron tomography led to the current view that these membrane domains are connected by rather small tubular structures, termed crista junctions. They have been proposed to regulate the dynamic distribution of proteins and lipids as well as of soluble metabolites between individual mitochondrial subcompartments. One example is the release of cytochrome
c upon induction of apoptosis. However, only little is known on the molecular mechanisms mediating the formation and maintenance of cristae and crista junctions. Here we review the current knowledge of the factors that determine cristae morphology and how the latter is linked to mitochondrial function. Further, we formulate several theoretical models which could account for the de novo formation of cristae as well as their propagation from existing cristae.
To determine the influence of the surface roughness on the friction and wear behavior, there are only limited experimental possibilities available. Due to the manufacturing process, the variation of ...the roughness also causes a change of the waviness and of the boundary layer of a surface. Thus, the roughness cannot be taken in isolation. It is therefore the objective of the present work to investigate the influence of the surface roughness on the running-in behavior with a numerical model, using the finite element method.
All calculations have been carried out with the finite element software ABAQUS in combination with the programming language PYTHON. They are based on a mixed-lubrication model, which was extended by a wear routine. This routine enables the calculation of local wear depths on both tribological partners in non-lubricated and lubricated regimes. For modelling the local wear depths, the surface nodes of the finite element mesh were adjusted by a modified wear law based on Archard. In first investigations, the influence of different manufacturing processes on the wear behavior was determined.
•Modelling wear on rough surfaces by using the wear law by Archard on the microscale.•Scaling wear depths for modelling the wear and friction behaviour of the running-in.•Investigation of the influence of the surface roughness on the running-in behavior.•Investigation of the friction behavior of lubricated contacts in the running-in.
The incidence of numerous types of cancer has been increasing over recent years, representing the second-most frequent cause of death after cardiovascular diseases. Even though, the number of ...effective anticancer drugs is increasing as well, a large number of patients suffer from severe side effects (e.g., cardiomyopathies) caused by these drugs. This adversely affects the patients' well-being and quality of life. On the molecular level, tumor cells that survive treatment modalities can become chemotherapy-resistant. In addition, adverse impacts on normal (healthy, stromal) cells occur concomitantly. Strategies that minimize these negative impacts on normal cells and which at the same time target tumor cells efficiently are needed. Recent studies suggest that redox-based combinational nanotherapies may represent one option in this direction. Here, we discuss recent advances in the application of nanoparticles, alone or in combination with other drugs, as a promising anticancer tool. Such novel strategies could well minimize harmful side effects and improve patients' health prognoses.
The sensory bias hypothesis proposes that female preferences for male sexual signalling traits evolved in contexts other than mating. Individuals of both sexes may experience similar selection ...pressures in these contexts; thus males may have similar biases to females for variation in signal traits. We tested this prediction in the grey treefrog,
Hyla chrysoscelis
, in which males produce simple advertisement calls, but females are more attracted to certain novel complex stimuli. We recorded males' responses to playbacks of both simple advertisement calls and complex calls consisting of the advertisement call with an acoustic appendage (filtered noise, or heterospecific call pulses) either leading or following the call. We tested females’ preferences for the same stimuli in phonotaxis tests. We found evidence for a sensory bias in both sexes: males gave more aggressive calls in response to complex stimuli and females sometimes preferred complex over simple calls. These biases were not universal and depended on both temporal order and appendage characteristics, but how these effects manifested differed between the sexes. Ultimately, our approach of studying biases of both sexes in response to novel mating signals will shed light on the origin of mating preferences, and the mechanisms by which sensory biases operate.
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