A5042587021- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Axon Guidance and Neuronal Signaling
- Developmental Biology and Gene Regulation
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Angiogenesis and VEGF in Cancer
- Wnt/β-catenin signaling in development and cancer
- Infectious Diseases and Mycology
- Genetics and Neurodevelopmental Disorders
- Apelin-related biomedical research
- Advanced Proteomics Techniques and Applications
- Cancer-related molecular mechanisms research
- Connective Tissue Growth Factor Research
- Metabolomics and Mass Spectrometry Studies
- Neurological diseases and metabolism
DKFZ-ZMBH Alliance
2024
Heidelberg University
2024
Izmir Institute of Technology
2015-2022
University of Freiburg
2017-2021
Abstract The mitochondrial proteome comprises ~1000 (yeast)–1500 (human) different proteins, which are distributed into four subcompartments. sublocalization of these proteins within the organelle in most cases remains poorly defined. Here we describe an integrated approach combining stable isotope labeling, various protein enrichment and extraction strategies quantitative mass spectrometry to produce a map submitochondrial distribution S. cerevisiae . This landscape enables proteome-wide...
The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly cleavable presequences. Presequence processing upon essential for proteostasis and survival, but the consequences dysfunctional protein maturation unknown. We find that impaired presequence causes accumulation precursors inside mitochondria form aggregates, escape degradation unexpectedly do not cause cell death. Instead, cells survive via activation a unfolded response (mtUPR)-like...
The translocase of the outer mitochondrial membrane TOM constitutes organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, presents ideal target to adjust proteome upon changing cellular demands. Here, we identify that import receptor TOM70 is targeted by kinase DYRK1A and this modification plays a critical role in activation carrier pathway. Phosphorylation
The mitochondrial proteome is built and maintained mainly by import of nuclear‐encoded precursor proteins. Most these precursors use N‐terminal presequences as targeting signals that are removed matrix proteases. essential processing protease MPP cleaves after into the organelle thereby enabling protein folding functionality. cleaved subsequently degraded peptidases. While most processes have been discovered in yeast, characterization human enzymes still scarce. As presequence peptidase PreP...
IRF6, a member of Interferon Regulatory Factors (IRF) family, is involved in orofacial and epidermal development. In breast cancer cell lines ectopic expression IRF6 reduces numbers suggesting role as negative regulator cycle. direct target canonical Notch signaling keratinocyte differentiation. luminal fate determination stem regulation the normal implicated an oncogene cancer. activation sufficient to induce proliferation transformation non-tumorigenic epithelial line, MCF10A. ΔNp63, which...
Approximately 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which cleaved upon exposure to processing protease MPP in matrix. Cleaved presequence peptides then need be efficiently degraded, and impairment this clearance step, for example, by amyloid β peptides, causes feedback inhibition MPP, leading ultimately accumulation immature within mitochondria. Degradation is performed Cym1 yeast its homologue, PreP, humans. Here we identify novel...
Semaphorin 6D (SEMA6D), a member of the class 6 semaphorin family, is membrane-associated protein that plays key role in development cardiac and neural tissues. A growing body evidence suggests SEMA6D also involved tumorigenesis. In breast cancer, high levels are correlated with better survival rates. However, very little known about functional significance present study, we aimed to investigate effects expression on normal cell line MCF10A cancer lines MCF7 MDA MB 231. We demonstrated...
Metastasis is the main reason for death in breast cancer. Understanding molecular players metastasis crucial diagnostic and therapeutic purposes. Notch signalling plays an oncogenic role tumorigenesis involved metastasis. Downstream mediators of prometastatic processes are not yet fully discovered. Here we aimed to investigate whether regulates expression SEMA3C, HMGA2, CXCL14, CXCR7, CCL20, which processes, cell lines. To this end, selected genes was analysed following activation by...