A5076023386- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Mitochondrial Function and Pathology
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Lipid metabolism and biosynthesis
- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Neonatal Health and Biochemistry
- Cancer, Hypoxia, and Metabolism
- Photosynthetic Processes and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
Rockefeller University
2023-2024
Universitätsmedizin Göttingen
2016-2020
European Neuroscience Institute Göttingen
2018-2020
Max Planck Society
2019-2020
University Medical Center
2018
Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired remain poorly understood. We show here that inhibition triggers cellular iron deficiency, which results in mitochondrial function non-apoptotic cell death. These effects are recovered supplying via lysosome-independent pathway. Notably, deficiency sufficient trigger inflammatory signaling...
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...
Mitochondria and lysosomes are two organelles that carry out both signaling metabolic roles in cells. Recent evidence has shown mitochondria dependent on one another, as primary defects cause secondary the other. Although there functional impairments cases, consequences of mitochondrial dysfunction lysosomal dissimilar. Here, we used RNA sequencing to obtain transcriptomes from cells with or identify global cellular associated dysfunction. We these data determine pathways affected by...
Abstract Membrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms protein-induced curvature have been described in some detail. Contrary, the effect that physico-chemical properties of on these processes far less well understood. Here, we show binding and curvature-inducing ENTH domain epsin1 regulated by phosphatidylserine (PS). binds to membranes PI(4,5)P 2 -dependent manner but only induces...
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...
Mitochondria and lysosomes are two organelles that carry out both signaling metabolic roles in the cells. Recent evidence has shown mitochondria dependent on one another, as primary defects cause secondary other. Nevertheless, consequences of mitochondrial malfunction lysosomal not similar, despite cases there impairments lysosomes. Here, we used RNA sequencing to obtain transcriptomes from cells with or defects, identify what global cellular associated We these data determine pathways...
SUMMARY Lysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired remain unknown. We show here that inhibition triggers cellular iron deficiency, which results in mitochondrial function necrotic cell death. These effects are recovered supplying via lysosome-independent pathway. Notably, deficiency sufficient trigger inflammatory signaling cultured...
SUMMARY Efficient communication between mitochondria and the nucleus underlies homoeostatic metabolic control, though involved mitochondrial factors their mechanisms are poorly defined. Here, we report surprising detection of multiple mitochondrial-derived transfer RNAs (mito-tRNAs) within nuclei human cells. Focused studies nuclear-transported mito-tRNA-asparagine (mtAsn) revealed that its cognate charging enzyme (NARS2) is also present in nucleus. MtAsn promoted interaction NARS2 with...
Abstract Membrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms protein induced curvature have been described in some detail. Contrary, the effect that physico-chemical properties of has on these processes far less well understood. Here, we show binding and curvature-inducing ENTH domain epsin1 regulated by phosphatidylserine (PS). binds to membranes PI(4,5)P 2 -dependent manner but only induces...