A5032708501- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Photosynthetic Processes and Mechanisms
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Cancer, Hypoxia, and Metabolism
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Marine Toxins and Detection Methods
- Genetic Neurodegenerative Diseases
- Retinal Development and Disorders
- Historical and Religious Studies of Rome
- Neural dynamics and brain function
- Historical and Architectural Studies
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Photoreceptor and optogenetics research
- Coconut Research and Applications
- Cerebrovascular and genetic disorders
- Cardiomyopathy and Myosin Studies
- Peptidase Inhibition and Analysis
Heinrich Heine University Düsseldorf
2015-2024
Düsseldorf University Hospital
2021-2024
University of Cologne
2012-2014
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2014
Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage YME1L OMA1 at two distinct sites leads to accumulation of both long short forms maintains mitochondrial fusion. Stress-induced processing converts completely into isoforms, inhibits fusion, triggers fragmentation. Here, we have analyzed function different in cells lacking YME1L, OMA1, or both. Unexpectedly, deletion Oma1 restored...
Article14 October 2019Open Access Source DataTransparent process Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent Dane M Wolf Department of Medicine (Endocrinology), Molecular Medical Pharmacology, David Geffen School Medicine, University California, Los Angeles, CA, USA Graduate Program in Nutrition Metabolism, Sciences, Boston Boston, MA, Search for more papers by this author Mayuko Segawa Arun Kumar Kondadi Institute...
Article18 February 2020Open Access Transparent process Cristae undergo continuous cycles of membrane remodelling in a MICOS-dependent manner Arun Kumar Kondadi orcid.org/0000-0002-5888-7834 Institute Biochemistry and Molecular Biology I, Medical Faculty, Heinrich Heine University Düsseldorf, Germany Search for more papers by this author Ruchika Anand orcid.org/0000-0001-7337-6007 Sebastian Hänsch Faculty Mathematics Natural Sciences, Center Advanced Imaging, Jennifer Urbach...
The stress-responsive mitochondrial sirtuin SIRT4 controls cellular energy metabolism in a NAD+-dependent manner and is implicated senescence aging. Here we reveal novel function of morphology/quality control regulation mitophagy. We report that moderate overexpression SIRT4, but not its enzymatically inactive mutant H161Y, sensitized cells to stress. CCCP-triggered dissipation the membrane potential resulted increased ROS levels autophagic flux, surprisingly led mass decreased...
Mitochondrial cristae are connected to the inner boundary membrane via crista junctions which implicated in regulation of oxidative phosphorylation, apoptosis, and import lipids proteins. The MICOS complex determines formation junctions. We performed complexome profiling identified Mic13, also termed Qil1, as a subunit complex. show that MIC13 is an protein physically interacting with MIC60, central Using CRISPR/Cas method we generated first cell line deleted for MIC13. These knockout cells...
Brain organoids derived from human pluripotent stem cells are a promising tool for studying neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase regionalized organoids. We show that cBOS host mature neurons astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs action potential firing neurons. Spontaneous intracellular calcium signals...
Homologous apolipoproteins of MICOS complex, MIC26 and MIC27, show an antagonistic regulation their protein levels, making it difficult to deduce individual functions using a single gene deletion. We obtained double knockout (DKO) human cells MIC27 found that DKO more concentric onion-like cristae with loss CJs than any deletion indicating overlapping roles in formation CJs. Using combination complexome profiling, STED nanoscopy, blue-native gel electrophoresis, we are dispensable for the...
Remodeling of mitochondrial ultrastructure is a process that critical for organelle physiology and apoptosis. Although the key players in this process-mitochondrial contact site cristae junction organizing system (MICOS) Optic Atrophy 1 (OPA1)-have been characterized, mechanisms behind its regulation remain incompletely defined. Here, we found addition to role division, metallopeptidase OMA1 required maintenance intermembrane connectivity through dynamic association with MICOS. This...
Abstract Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of RAS-MAPK pathway. Distinct variants, including recurrent Ser257Leu substitution RAF1, are associated with severe hypertrophic cardiomyopathy (HCM). Here, we investigated elusive mechanistic link between NS-associated RAF1 S257L and HCM using three-dimensional cardiac bodies bioartificial tissues generated from patient-derived induced pluripotent stem cells (iPSCs)...
Abstract APOO/MIC26 is a subunit of the MICOS complex required for mitochondrial cristae morphology and function. Here, we report novel variant gene that causes severe disease with overall progeria‐like phenotypes in two patients. Both patients developed partial agenesis corpus callosum, bilateral congenital cataract, hypothyroidism, immune deficiencies. The died at an early age 12 or 18 months. Exome sequencing revealed mutation (NM_024122.5): c.532G>T (p.E178*) nonsense leading to loss...
Abstract Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, buffering cytosolic Ca 2+ initiation apoptosis. Compounds that interfere these termed mitochondrial toxins, many which derived from microbes, such as antimycin A, oligomycin ionomycin. Here, we identify mycotoxin phomoxanthone A (PXA), endophytic fungus Phomopsis longicolla , a toxin. We show PXA elicits strong release mitochondria but not ER. In addition, depolarises similarly to...
Abstract Expansion of the glutamine tract (poly-Q) in protein huntingtin (HTT) causes neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into neurodevelopmental impact human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic 70Q expansion remove poly-Q HTT. The introduction mutation caused aberrant development cerebral organoids with loss...
Mitochondria play central roles in metabolism and metabolic disorders such as type 2 diabetes. MIC26, a mitochondrial contact site cristae organising system complex subunit, was linked to diabetes modulation of lipid metabolism. Yet, the functional role MIC26 regulating under hyperglycemia is not understood. We used multi-omics approach combined with assays using WT KO cells cultured normoglycemia or hyperglycemia, mimicking altered nutrient availability. show that has an inhibitory...
Impairments of mitochondrial functions are linked to human ageing and pathologies such as cancer, cardiomyopathy, neurodegeneration diabetes. Specifically, aberrations in ultrastructure inner membrane (IM) factors regulating them The development diabetes is connected the ‘Mitochondrial Contact Site Cristae Organising System’ (MICOS) complex which a large protein defining IM architecture. MIC26 MIC27 homologous apolipoproteins MICOS complex. has been reported 22 kDa 55 glycosylated secreted...
Cristae membranes have been recently shown to undergo intramitochondrial merging and splitting events. Yet, the metabolic bioenergetic factors regulating them are unclear. Here, we investigated whether how cristae morphology dynamics dependent on oxidative phosphorylation (OXPHOS) complexes, mitochondrial membrane potential (ΔΨ m ), ADP/ATP nucleotide translocator. Advanced live-cell STED nanoscopy combined with in-depth quantification were employed analyse after treatment of mammalian cells...
Abstract Autophagy is an intracellular recycling pathway with implications for homeostasis and cell survival. Its pharmacological modulation can aid chemotherapy by sensitizing cancer cells toward approved drugs overcoming chemoresistance. Recent translational data on autophagy modulators show promising results in reducing tumor growth metastasis, but also reveal a need more specific compounds novel lead structures. Here, we searched such autophagy-modulating flow cytometry-based...
Abstract Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of RAS-MAPK pathway. Distinct variants, including recurrent Ser257Leu substitution RAF1, are associated with severe hypertrophic cardiomyopathy (HCM). Here, we investigated elusive mechanistic link between NS-associated RAF1S257L and HCM using three-dimensional cardiac bodies bioartificial tissues generated from patient-derived induced pluripotent stem cells (iPSCs)...