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Functional Coupling of Presequence Processing and Degradation in Human Mitochondria
Abstract: The mitochondrial proteome is built and maintained mainly by import of nuclear-encoded precursor proteins. Most of these precursors use N-terminal presequences as targeting signals that are removed by mitochondrial matrix proteases. The essential mitochondrial processing protease MPP cleaves presequences after import into the organelle thereby enabling protein folding and functionality. The cleaved presequences are subsequently degraded by peptidases. While most of these processes have been discovered in yeast, characterization of the human enzymes is still scarce. As the matrix presequence peptidase PreP has been reported to play a role in Alzheimer's disease, analysis of impaired...
Mitochondrial DNA
This volume compiles a comprehensive range of methods to study key aspects of mitochondrial DNA including nucleoid structure and packaging, replication, genome integrity, and disease. Chapters are organized into eight methodological sections that cover in vitro and in vivo methods, including for mtDNA isolation, visualization, deep sequencing, gene editing, and diagnostic aspects of mtDNA disease. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and methods, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Mitochondrial DNA: Methods and Protocols aims to be useful and informative for researchers and clinicians with an interest in mitochondrial DNA.
An Early MtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects Against Intramitochondrial Proteotoxic Aggregates
Abstract: The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense
Weight Management
Weight management is a multi- and cross-disciplinary challenge. This book covers many etiological and diagnostic aspects of weight-related disorders and their treatment. This book explains how body weight influences and is influenced by the brain, hormones and immune system, diet, physical activity, posture and gait, and the social environment. This book also elucidates the health consequences of significantly low or pathologically increased body weight. Furthermore, ideas on how to influence and manage body weight including anti-obesity medical devices, diet counselling, artificial sweeteners, prebiotics and probiotics, proanthocyanidins, bariatric surgery, microbiota transplantation, warming, physical exercise, music and psychological therapy are discussed.
Econometrics of Structural Change
Econometric models are made up of assumptions which never exactly match reality. Among the most contested ones is the requirement that the coefficients of an econometric model remain stable over time. Recent years have therefore seen numerous attempts to test for it or to model possible structural change when it can no longer be ignored. This collection of papers from Empirical Economics mirrors part of this development. The point of departure of most studies in this volume is the standard linear regression model Yt = x;fJt + U (t = I, ... , 1), t where notation is obvious and where the index t emphasises the fact that structural change is mostly discussed and encountered in a time series context. It is much less of a problem for cross section data, although many tests apply there as well. The null hypothesis of most tests for structural change is that fJt = fJo for all t, i.e. that the same regression applies to all time periods in the sample and that the disturbances u are well behaved. The well known Chow test for instance assumes t that there is a single structural shift at a known point in time, i.e. that fJt = fJo (t
