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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
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...
Cellular Lipid Metabolism
For years lipids have fascinated cell biologists and biochemists due to their profound effects on cell function. "Cellular Lipid Metabolism" highlights new concepts and recent findings, but also reviews important discoveries made in the past. Outstanding international experts contribute 13 chapters on the genetics, molecular and cell biology of lipids. Presenting analyses at the molecular level they reveal the principles by which cellular lipid metabolism functions. Further, numerous intriguing observations that cannot yet be explained are identified, stimulating the readers to future studies. This book provides an invaluable source of information for biomedical researchers in energy metabolism, vascular biology, endocrinology and lipidology.
Oxford Guide to Effective Writing and Speaking
The Oxford Guide to Effective Writing & Speaking is the essential guide for everyone who needs to communicate clearly and effectively. It combines practical advice on specific writing and speaking tasks with detailed self-help chapters covering grammar, spelling, and the writing process itself.
