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Volume 4, Issue 8, pp. 236 - 277, August 2017

Issue cover
Cover: The image shows a blood agar plate culture with Haemophilus influenzae satelliting around Staphylococcus aureus (image by Dr. Mike Miller, Center for Disease Control and Prevention, USA and obtained via the CDC Public Health Image Library , ID#1047); image modified by MIC. The cover is published under the Creative Commons Attribution (CC BY) license. Enlarge issue cover


The Yin & Yang of Mitochondrial Architecture – Interplay of MICOS and F1Fo-ATP synthase in cristae formation

Heike Rampelt and Martin van der Laan

page 236-239 | 10.15698/mic2017.08.583 | Full text | PDF | Abstract

Oxidative phosphorylation takes place at specialized compartments of the inner mitochondrial membrane, the cristae. The elaborate ultrastructure of cristae membranes enables efficient chemi-osmotic coupling of respiratory chain and F1Fo-ATP synthase. Dynamic membrane remodeling allows mitochondria to adapt to changing physiological requirements. The mitochondrial contact site and cristae organizing system (MICOS) and the oligomeric ATP synthase have been known to govern distinct features of cristae architecture. A new study [1] on the crosstalk between these two machineries now sheds light on the mechanisms of cristae formation and maintenance.


Integrative metabolomics as emerging tool to study autophagy regulation

Sarah Stryeck, Ruth Birner-Gruenberger, Tobias Madl

page 240-258 | 10.15698/mic2017.08.584 | Full text | PDF | Abstract

Recent technological developments in metabolomics research have enabled in-depth characterization of complex metabolite mixtures in a wide range of biological, biomedical, environmental, agricultural, and nutritional research fields. Nuclear magnetic resonance spectroscopy and mass spectrometry are the two main platforms for performing metabolomics studies. Given their broad applicability and the systemic insight into metabolism that can be obtained it is not surprising that metabolomics becomes increasingly popular in basic biological research. In this review, we provide an overview on key metabolites, recent studies, and future opportunities for metabolomics in studying autophagy regulation. Metabolites play a pivotal role in autophagy regulation and are therefore key targets for autophagy research. Given the recent success of metabolomics, it can be expected that metabolomics approaches will contribute significantly to deciphering the complex regulatory mechanisms involved in autophagy in the near future and promote understanding of autophagy and autophagy-related diseases in living cells and organisms.

Research Articles

Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10

Katharina Eydt, Karen M. Davies, Christina Behrendt, Ilka Wittig and Andreas S. Reichert

page 259-272 | 10.15698/mic2017.08.585 | Full text | PDF | Abstract

The inner boundary and the cristae membrane are connected by pore-like structures termed crista junctions (CJs). The MICOS complex is required for CJ formation and enriched at CJs. Here, we address the roles of the MICOS subunits Mic27 and Mic10. We observe a positive genetic interaction between Mic27 and Mic60 and deletion of Mic27 results in impaired formation of CJs and altered cristae membrane curvature. Mic27 acts in an antagonistic manner to Mic60 as it promotes oligomerization of the F1FO-ATP synthase and partially restores CJ formation in cells lacking Mic60. Mic10 impairs oligomerization of the F1FO-ATP synthase similar to Mic60. Applying complexome profiling, we observed that deletion of Mic27 destabilizes the MICOS complex but does not impair formation of a high molecular weight Mic10 subcomplex. Moreover, this Mic10 subcomplex comigrates with the dimeric F1FO-ATP synthase in a Mic27-independent manner. Further, we observed a chemical crosslink of Mic10 to Mic27 and of Mic10 to the F1FO-ATP synthase subunit e. We corroborate the physical interaction of the MICOS complex and the F1FO-ATP synthase. We propose a model in which part of the F1FO-ATP synthase is linked to the MICOS complex via Mic10 and Mic27 and by that is regulating CJ formation.


Out with the old: Hsp90 finds amino acid residue more useful than co-chaperone protein

Abbey D. Zuehlke and Leonard Neckers

page 273-274 | 10.15698/mic2017.08.586 | Full text | PDF | Abstract

Redundant functions maintained from single to multicellular organisms have made Saccharomyces cerevisiae an important model for the analysis of conserved complex cellular processes. Yeast have been especially useful in understanding the regulation and function of the essential molecular chaperone, Heat Shock Protein 90 (Hsp90). Research focused on Hsp90 has determined that it is highly regulated by both co-chaperones and posttranslational modifications. A recent study per-formed by (Zuehlke et al., 2017) demonstrates that the function of one co-chaperone in yeast is replaced by posttranslational modification (PTM) of a single amino acid within Hsp90 in higher eukaryotes.

Having your cake and eating it – Staphylococcus aureus small colony variants can evolve faster growth rate without losing their antibiotic resistance

Gerrit Brandis, Sha Cao, Douglas L. Huseby and Diarmaid Hughes

page 275-277 | 10.15698/mic2017.08.587 | Full text | PDF | Abstract

Staphylococcus aureus can produce small colony variants (SCVs) during infections. These cause significant clinical problems because they are difficult to detect in standard microbiological screening and are associated with persistent infections. The major causes of the SCV phenotype are mutations that inhibit respiration by inactivation of genes of the menadione or hemin biosynthesis pathways. This reduces the production of ATP required to support fast growth. Importantly, it also decreases cross-membrane potential in SCVs, resulting in decreased uptake of cationic compounds, with reduced susceptibility to aminoglycoside antibiotics as a consequence. Because SCVs are slow-growing (mutations in men genes are associated with growth rates in rich medium ~30% of the wild-type growth rate) bacterial cultures are very susceptible to rapid takeover by faster-growing mutants (revertants or suppressors). In the case of reversion, the resulting fast growth is obviously associated with the loss of antibiotic resistance. However, direct reversion is relatively rare due to the very small genetic target size for such mutations. We explored the phenotypic consequences of SCVs evolving faster growth by routes other than direct reversion, and in particular whether any of those routes allowed for the maintenance of antibiotic resistance. In a recent paper (mBio 8: e00358-17) we demonstrated the existence of several different routes of SCV evolution to faster growth, one of which maintained the antibiotic resistance phenotype. This discovery suggests that SCVs might be more adaptable and problematic that previously thought. They are capable of surviving as a slow-growing persistent form, before evolving into a significantly faster-growing form without sacrificing their antibiotic resistance phenotype.