A5004089795- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Calcium signaling and nucleotide metabolism
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Neonatal Health and Biochemistry
- Alzheimer's disease research and treatments
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Trypanosoma species research and implications
- Cancer, Hypoxia, and Metabolism
Queen Mary University of London
2019-2021
William Harvey Research Institute
2019-2021
University of Göttingen
2019
University Medical Center
2018
Universitätsmedizin Göttingen
2016
Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a regulator of energy homeostasis) signaling in tissue cultured cells. The deactivation AMPK RC-deficiency is due to increased expression the AMPK-inhibiting FLCN (folliculin). found be necessary basal lysosomal function, inhibits function by...
Abstract Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial affects other organelles, particularly lysosomes. Here, we demonstrate that respiratory chain (RC) impairments elicit a stress pathway regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, effect of over depends on timeframe elicited: while RC inhibition with...
Perturbations in mitochondrial function and homeostasis are pervasive lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses biogenesis diseases Niemann-Pick type C (NPC) acid sphingomyelinase deficiency (ASM), patient cells mouse tissues. This mechanism is mediated by transcription factors KLF2 ETV1, which both induced NPC ASM cells. Mitochondrial defects these rescued silencing of or ETV1. Increased ETV1 expression...
Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence this rare underestimated due to delayed diagnosis. Moreover, management identified subjects often complicated detection variants unclear diagnostic interpretation, usually in screening studies. We performed an observational study based on biochemical and genetic analysis 805 dried blood spot samples from patients with clinical symptoms or family history pathology, which...
The autophagy-lysosomal pathway is impaired in many neurodegenerative diseases characterized by protein aggregation, but the link between aggregation and lysosomal dysfunction remains poorly understood. Here, we combine cryo-electron tomography, proteomics, cell biology studies to investigate effects of aggregates primary neurons. We use artificial amyloid-like β-sheet proteins (β proteins) focus on gain-of-function aspect aggregation. These form fibrillar cause neurotoxicity. show that late...
Abstract The autophagy-lysosomal pathway is impaired in many neurodegenerative diseases characterized by protein aggregation, but the link between aggregation and lysosomal dysfunction remains poorly understood. Here, we combine cryo-electron tomography, proteomics cell biology studies to investigate effects of aggregates primary neurons. We use artificial amyloid-like β-sheet proteins (β proteins) focus on gain-of-function aspect aggregation. These form fibrillar cause neurotoxicity. show...
Perturbations in mitochondrial function and homeostasis are pervasive lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses biogenesis diseases Niemann-Pick type C (NPC) acid sphingomyelinase deficiency (ASM), patient cells mouse tissues. This mechanism is mediated by transcription factors KLF2 ETV1, which both induced NPC ASM cells. Mitochondrial defects these rescued silencing of or ETV1. Increased ETV1 expression...