bims-resufa 2019-07-07 papers

Issue of 2019–07–07
three papers selected by
Vera Strogolova, Marquette University

J Anim Sci. 2019 Jun 27. pii: skz219. [Epub ahead of print]

Oxidative stress and efficiency: The tightrope act of mitochondria in health and disease.

Oxidative stress is an unavoidable consequence of aerobic metabolism. Whereas high amounts of mitochondrial reactive oxygen species (ROS) can cause oxidation, low levels play important roles in signal transduction. In a Pedigree male (PedM) broiler model of feed efficiency (FE), the low FE phenotype was characterized by increased ROS in isolated mitochondria (muscle, liver, and duodenum) with a pervasive protein oxidation in mitochondria and tissues. Subsequent proteogenomic studies in muscle revealed evidence of enhanced mitoproteome abundance enhanced mitochondrial phosphocreatine shuttling expression, and enhanced ribosome assembly in the high FE phenotype. Surprisingly, an enhanced infrastructure would foster greater repair of damaged proteins or organelles through the autophagy and proteosome pathways in the high FE phenotype. Although protein and organelle degradation, recycling, and reconstruction would be energetically expensive, it is possible that energy invested into maintaining optimal function of proteins and organelles contributes to cellular efficiency in the high FE phenotype. New findings in mitochondrial physiology have been reported in the last several years. Reverse electron transport (RET), once considered an artifact of in vitro conditions, now is recognized to play significant roles in inflammation, ischemia-reperfusion, muscle differentiation, and energy utilization. A topology of ROS production indicates that ROS derived from Complex I of the respiratory chain primarily causes oxidation, whereas ROS generated from Complex III are primarily involved in cell signaling. It is also apparent that there is a constant fission and fusion process that mitochondria undergo that help maintain optimal mitochondrial function and enables mitochondria to adjust to periods of nutrient limitation and nutrient excess. Understanding the balancing act that mitochondria play in health and disease will continue to be a vital biological component in health-production efficiency and disease in commercial animal agriculture.

Keywords: Mitochondrial biology; feed efficiency; mitochondrial dynamics; oxidative stress

DOI: https://doi.org/10.1093/jas/skz219

Biochim Biophys Acta Bioenerg. 2019 Jun 24. pii: S0005-2728(19)30066-0. [Epub ahead of print]

Mitochondrial cristae narrowing upon higher 2-oxoglutarate load.

Andrea Dlasková, Tomáš Špaček, Hana Engstová, Jitka Špačková, Adam Schröfel, Blanka Holendová, Katarína Smolková, Lydie Plecitá-Hlavatá, Petr Ježek.

Hypoxia causes mitochondrial cristae widening, enabled by the ~20% degradation of Mic60/mitofilin, with concomitant clustering of the MICOS complex, reflecting the widening of crista junctions (outlets) (Plecitá-Hlavatá et al. FASEB J., 2016 30:1941-1957). Attempting to accelerate metabolism by the addition of membrane-permeant dimethyl-2-oxoglutarate (dm2OG) to HepG2 cells pre-adapted to hypoxia, we found cristae narrowing by transmission electron microscopy. Glycolytic HepG2 cells, which downregulate hypoxic respiration, instantly increased respiration with dm2OG. Changes in intracristal space (ICS) morphology were also revealed by 3D super-resolution microscopy using Eos-conjugated ICS-located lactamase-β. Cristae topology was resolved in detail by focused-ion beam/scanning electron microscopy (FIB/SEM). The spatial relocations of key cristae-shaping proteins were indicated by immunocytochemical stochastic 3D super-resolution microscopy (dSTORM), while analyzing inter-antibody-distance histograms: i) ATP-synthase dimers exhibited a higher fraction of shorter inter-distances between bound F1-α primary Alexa-Fluor-647-conjugated antibodies, indicating cristae narrowing. ii) Mic60/mitofilin clusters (established upon hypoxia) decayed, restoring isotropic random Mic60/mitofilin distribution (a signature of normoxia). iii) outer membrane SAMM50 formed more focused clusters. Less abundant fractions of higher ATP-synthase oligomers of hypoxic samples on blue-native electrophoresis became more abundant fractions at the high dm2OG load and at normoxia. This indicates more labile ATP-synthase dimeric rows established at crista rims upon hypoxia, strengthened at normoxia or dm2OG-substrate load. Hypothetically, the increased Krebs substrate load stimulates the cross-linking/strengthening of rows of ATP-synthase dimers at the crista rims, making them sharper. Crista narrowing ensures a more efficient coupling of proton pumping to ATP synthesis. We demonstrated that cristae morphology changes even within minutes.

Keywords: 3D super-resolution microscopy; ATP-synthase dimers; Dimethyl-2-oxoglutarate; Direct stochastic optical reconstruction microscopy; Hypoxia; Mic60/mitofilin; Mitochondrial cristae; dSTORM

DOI: https://doi.org/10.1016/j.bbabio.2019.06.015

Mitochondrion. 2019 Jun 25. pii: S1567-7249(19)30022-4. [Epub ahead of print]

Dynamic of mitochondrial network, cristae, and mitochondrial nucleoids in pancreatic β-cells.

Petr Ježek, Andrea Dlasková.

Type 2 diabetes progression stems from dysfunction of β-cells, besides the peripheral insulin resistance. Mitochondria as glucose sensor and regulation center are impaired at various stages of this progression. Their biogenesis and functional impairment is reflected by altered morphology of the mitochondrial network and ultramorphology of cristae and mitochondrial DNA loci, termed nucleoids. Aspects of all above changes are reviewed here together with a brief introduction to proteins involved in mitochondrial network dynamics, cristae shaping, and mtDNA nucleoid structure and maintenance. Most frequently, pathology is reflected by the fragmentation of network, cristae inflation or absence and declining number of nucleoids.

Keywords: Mitochondrial cristae; Mitochondrial network; Mitochondrial nucleoids; Type 2 diabetes

DOI: https://doi.org/10.1016/j.mito.2019.06.007