Achieving Sustainable Mobility. The Discontinuation of the Socio-Technical Regime of Automobility

So far, research on sustainable transitions has predominantly focussed on the management of innovation processes and mostly neglected that political decision-making has also to consider the discontinuation of the established socio-technical regime. We will present a case study on the automobility regime as an example of discontinuation governance “in the making”. Analysing policies and actor constellations on local, national, and supranational levels, we try to figure out strategies and measures that have been applied to (politically) challenge the automobility regime. Additionally, we propose combining three analytical models in order to grasp these developments, namely the multi-level perspective (MLP), the multi-level governance (MLG) and actor-centred approaches

Governance of Discontinuation – Neue Perspektiven auf die Energiewende und nachhaltige Mobilität

Bisher steht bei Studien zum Wandel sozio-technischer Systeme zumeist die Governance von Innovationen im Vordergrund. Unbeachtet bleibt häufig, dass die Lösung gesellschaftlicher Probleme nicht allein in der Entwicklung von neuen, sondern auch in der Abschaffung von etablierten sozio-technischen Systemen bestehen kann. Geleitet von der zentralen Annahme, dass sich sozio-technische Systeme nicht ausschließlich durch die Entwicklung innovativer, durchsetzungsfähiger Alternativen beenden lassen, schlagen wir folgenden Perspektivwechsel vor: Zur Untersuchung des sozio-technischen Wandels muss der Blick auch auf die gezielte Beendigung bestehender Systeme und Strukturen gelenkt werden

The Disulfide Relay of the Intermembrane Space Oxidizes the Ribosomal Subunit Mrp10 on Its Transit into the Mitochondrial Matrix

SummaryMost mitochondrial proteins are synthesized in the cytosol and directed into the organelle; matrix proteins contain presequences that guide them through translocases in contact sites of the outer and inner membrane. In contrast, the import of many intermembrane space proteins depends on cysteine residues and the oxidoreductase Mia40. Here, we show that both import machineries can cooperate in the biogenesis of matrix proteins. Mrp10, a conserved protein of the mitochondrial ribosome, interacts with Mia40 during passage into the matrix. Mrp10 contains an unconventional proline-rich matrix-targeting sequence that renders import intermediates accessible to Mia40. Although oxidation of Mrp10 is not essential for its function in mitochondrial translation, the disulfide bonds prevent proteolytic degradation of Mrp10 and thereby counteract instability of the mitochondrial genome. The unconventional import pathway of Mrp10 is presumably part of a quality-control circle that connects mitochondrial ribosome biogenesis to the functionality of the mitochondrial disulfide relay

Quantitative persulfide site identification (qPerS-SID) reveals protein targets of H2S releasing donors in mammalian cells

H2S is an important signalling molecule involved in diverse biological processes. It mediates the formation of cysteine persulfides (R-S-SH), which affect the activity of target proteins. Like thiols, persulfides show reactivity towards electrophiles and behave similarly to other cysteine modifications in a biotin switch assay. In this manuscript, we report on qPerS-SID a mass spectrometry-based method allowing the isolation of persulfide containing peptides in the mammalian proteome. With this method, we demonstrated that H2S donors differ in their efficacy to induce persulfides in HEK293 cells. Furthermore, data analysis revealed that persulfide formation affects all subcellular compartments and various cellular processes. Negatively charged amino acids appeared more frequently adjacent to cysteines forming persulfides. We confirmed our proteomic data using pyruvate kinase M2 as a model protein and showed that several cysteine residues are prone to persulfide formation finally leading to its inactivation. Taken together, the site-specific identification of persulfides on a proteome scale can help to identify target proteins involved in H2S signalling and enlightens the biology of H2S and its releasing agents

The zinc-binding protein Hot13 promotes oxidation of the mitochondrial import receptor Mia40

A disulphide relay system mediates the import of cysteine-containing proteins into the intermembrane space of mitochondria. This system consists of two essential proteins, Mia40 and Erv1, which bind to newly imported proteins by disulphide transfer. A third component, Hot13, was proposed to be important in the biogenesis of cysteine-rich proteins of the intermembrane space, but the molecular function of Hot13 remained unclear. Here, we show that Hot13, a conserved zinc-binding protein, interacts functionally and physically with the import receptor Mia40. It improves the Erv1-dependent oxidation of Mia40 both in vivo and in vitro. As a consequence, in mutants lacking Hot13, the import of substrates of Mia40 is impaired, particularly in the presence of zinc ions. In mitochondria as well as in vitro, Hot13 can be functionally replaced by zinc-binding chelators. We propose that Hot13 maintains Mia40 in a zinc-free state, thereby facilitating its efficient oxidation by Erv1

Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol

Sod1 is an important antioxidant enzyme that becomes activated by its chaperone, Ccs1. The localization of Ccs1 to mitochondria is controlled by the oxidoreductase Mia40. The formation of a disulfide bond between Cys-27 and Cys-64 in Ccs1 is critical for import and stability but not for Ccs1 activity in the maturation of Sod1