Looking for transitions

__Abstract__ Drawing on experience with transition monitoring in 9 different programmes and sectors in the period 2005-2010, his research describes a wide array of monitoring instruments as well as general building blocks for transition monitoring. Given the complexity and uncertainties regarding transitions, programmes generally do not start with well-defined objectives and a clear view of the transition they are pursuing. They develop these over time as well as the networks and innovations necessary to achieve them. Sometimes this ´goal searching´ behaviour is wrongly mistaken as a weakness of such programmes, as it makes it difficult to account for their impacts. However, Taanman finds that this behaviour is not only an emperical fact but also a strong legitimization for these programmes as it addresses key governance, market and system flaws. Transition monitoring supports programme development by providing facts, feedback and reflection on developments at project, programme and transition field levels. The research describes what kind of monitoring information is useful at different points in time as well as modes in which programme managers and outside experts can co-produce this information

Diffusion Paths for Micro Cogeneration Using Hydrogen in the Netherlands

We estimate the diffusion of micro cogeneration systems (MiCoGen) using hydrogen produced from natural gas in the Netherlands for the 2000-2050 period on the basis of economical factors. The diffusion is important for the transition to a hydrogen economy based on renewables, with natural gas paving the way for hydrogen from renewables which. For three scenarios full diffusion takes place in the period 2020-2050. The most important factors behind the diffusion are: growing energy demand, resulting in lower hydrogen costs and higher energy costs in the reference case and lower costs of MiCoGen stemming from learning economies. The model is very ad-vanced by considering all costs components for heterogeneous users which have been calculated for the entire diffusion period. It is the first threshold diffusion model that is being applied to the diffusion of technological clusters involving new or adapted infrastructures.diffusion model, hydrogen, hydrogen economy, micro cogeneration

NDUFA4 (Renamed COXFA4) Is a Cytochrome-c Oxidase Subunit

Groundbreaking work by Kadenbach and colleagues in the 1980s revealed the presence of 13 subunits in the mammalian mitochondrial cytochrome-c oxidase (COX; Complex IV). This observation stood the test of time until 2012 when it was demonstrated that NDUFA4, a polypeptide previously attributed to mitochondrial Complex I, was a 14th subunit of COX. In his recent opinion article, Kadenbach argued that NDUFA4 is not a subunit of COX. However, based on the findings that NDUFA4 deficiency results in a severe loss of COX activity and that NDUFA4 represents a stoichiometric component of the individual COX complex, we reason that NDUFA4 is a bona fide COX subunit and propose renaming it as COX subunit FA4 (COXFA4)

A LON-ClpP Proteolytic Axis Degrades Complex I to Extinguish ROS Production in Depolarized Mitochondria

Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson’s disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain. Complex I deficiency has also been identified in PD brain, and our study provides a compelling non-genetic mechanistic rationale to explain this observation: intact complex I depletes if mitochondrial bioenergetic capacity is robustly attenuated

Remodelling of the Mitochondrial Bioenergetic Pathways in Human Cultured Fibroblasts with Carbohydrates

Mitochondrial oxidative phosphorylation defects underlie many neurological and neuromuscular diseases. Patients’ primary dermal fibroblasts are one of the most commonly used in vitro models to study mitochondrial pathologies. However, fibroblasts tend to rely more on glycolysis than oxidative phosphorylation for their energy when cultivated in standard high-glucose medium, rendering it difficult to expose mitochondrial dysfunctions. This study aimed to systematically investigate to which extent the use of galactose- or fructose-based medium switches the fibroblasts’ energy metabolism to a more oxidative state. Highly proliferative cells depend more on glycolysis than less proliferative cells. Therefore, we investigated two primary dermal fibroblast cultures from healthy subjects: a highly proliferative neonatal culture and a slower-growing adult culture. Cells were cultured with 25 mM glucose, galactose or fructose, and 4 mM glutamine as carbon sources. Compared to glucose, both galactose and fructose reduce the cellular proliferation rate, but the galactose-induced drop in proliferation is much more profound than the one observed in cells cultivated in fructose. Both galactose and fructose result in a modest increase in mitochondrial content, including mitochondrial DNA, and a disproportionate increase in protein levels, assembly, and activity of the oxidative phosphorylation enzyme complexes. Galactose- and fructose-based media induce a switch of the prevalent biochemical pathway in cultured fibroblasts, enhancing aerobic metabolism when compared to glucose-based medium. While both galactose and fructose stimulate oxidative phosphorylation to a comparable degree, galactose decreases the cellular proliferation rate more than fructose, suggesting that a fructose-based medium is a better choice when studying partial oxidative phosphorylation defects in patients’ fibroblasts

Subunit composition of respiratory chain complex 1 and its responses to oxygen in mitochondria from human donor livers

OBJECTIVE: Donor liver function in transplantation is defined by mitochondrial function and the ability of mitochondria to recover from the sequence of warm and/or cold ischemia. Mitochondrial resilience maybe related to assembly and- subunit composition of Complex 1. The aim of this study was to determine if Complex 1 subunit composition was different in donor livers of varying quality and whether oxygen exposure had any effect. RESULTS: Five human livers not suitable for transplant were split. One half placed in cold static storage and the other half exposed to 40% oxygen for 2 h. Protein was extracted for western blot. Membranes were probed with antibodies against β-actin and the following subunits of Complex 1: MTND1, NDUFA10, NDUFB6 and NDUFV2. No difference in steady state Complex 1 subunit composition was demonstrated between donor livers of varying quality, in terms of steatosis or mode of donation. Neither did exposure to oxygen influence Complex 1 subunit composition. This small observational study on subunit levels suggest that Complex 1 is fully assembled as no degradation of subunits associated with the different parts of the enzyme was seen