A5068450352- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- Genetic Neurodegenerative Diseases
- GDF15 and Related Biomarkers
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- RNA modifications and cancer
- Mechanisms of cancer metastasis
- Metabolism and Genetic Disorders
- Anatomy and Medical Technology
- Vitamin C and Antioxidants Research
- RNA Research and Splicing
- Ferroptosis and cancer prognosis
- Mesenchymal stem cell research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Nicotinic Acetylcholine Receptors Study
- Cardiomyopathy and Myosin Studies
- Cell death mechanisms and regulation
- Photoreceptor and optogenetics research
Helmholtz Zentrum München
2023-2025
University of Padua
2014-2023
Neuroscience Institute
2014
Mitochondrial calcium accumulation was recently shown to depend on a complex composed of an inner-membrane channel (MCU and MCUb) regulatory subunits (MICU1, MCUR1, EMRE). A fundamental property MCU is low activity at resting cytosolic Ca(2+) concentrations, preventing deleterious cycling organelle overload. Here we demonstrate that these properties are ensured by heterodimer two proteins with opposite effects, MICU1 MICU2, which, both in purified lipid bilayers intact cells, stimulate...
Ca 2+ ions serve as pleiotropic second messengers in the cell, regulating several cellular processes. Mitochondria play a fundamental role homeostasis since mitochondrial (mitCa ) is key regulator of oxidative metabolism and cell death. MitCa uptake mediated by uniporter complex (MCUc) localized inner membrane (IMM). stimulates activity three enzymes Krebs cycle, thereby modulating ATP production promoting metabolism. As Paracelsus stated, “Dosis sola facit venenum,”in pathological...
Calcium (Ca
The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by the selective pore-forming subunit, (MCU), and accessory proteins, including MICU1, MICU2 EMRE. Their concerted action required to fine-tune uptake of into matrix which both sustains cell bioenergetics regulates apoptotic response. To adequately fulfil such requirements avoid impairment in handling, intracellular turnover all MCU components must be tightly regulated. Here we show that regulator but not MICU2,...
Abstract The mitochondrial calcium uniporter channel (MCUC) mediates entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of signaling networks their remodeling upon changes in activity not assessed. Here, we map interactome under resting conditions chronic loss or gain uptake. We identify 89 high-confidence interactors that link to complexes pathways, half which are associated with human disease. As a...
Parvalbumin (PV) is a cytosolic Ca2+-binding protein highly expressed in fast skeletal muscle, contributing to an increased relaxation rate. Moreover, PV "atrogene" downregulated most muscle atrophy conditions. Here, we exploit mice lacking explore the link between two functions. Surprisingly, ablation partially counteracts loss after denervation. Furthermore, acute downregulation accompanied by hypertrophy and upregulation atrophy. has minor impact on sarcoplasmic reticulum but associated...
MCUb is required for the phenotypic transition of macrophages that necessary skeletal muscle regeneration.
Abstract Creatine (Cr) is essential for cellular energy homeostasis, particularly in muscle and brain tissues. Transporter Deficiency (CTD), an X-linked disorder caused by mutations the SLC6A8 gene, disrupts Cr transport, leading to intellectual disability, speech delay, autism, epilepsy, various non-neurological symptoms. In addition neurological alterations, knockout (CrT −/y ) mice exhibit severe atrophy functional impairments. This study provides first characterization of skeletal...
Cells utilize protein disaggregases to avoid abnormal aggregation that causes many diseases. Among these, caseinolytic peptidase B homolog (CLPB) is localized in the mitochondrial intermembrane space and linked human disease. Upon CLPB loss, MICU1 MICU2, regulators of calcium uniporter complex (mtCU), OPA1, a main mediator fusion, become insoluble but functional outcome remains unclear. In this work we demonstrate required maintain signalling fusion dynamics. loss results altered mtCU...
Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating molecular identity physiological roles mitochondrial uniporter (MCU) complex, we now have tools to understand functions Ca2+ in regulation pathophysiological Herein, describe role key MCU complex components insulin resistance mouse human adipose tissue. Adipose tissue gene expression was analyzed from several models obese diabetic rodents 72 patients with...
Mice (Y522S or YS), carrying a mutation of the sarcoplasmic reticulum (SR) Ca2+ release channel skeletal muscle fibers (Ryanodine Receptor type-1, RyR1) which causes leak, are widely accepted and intensively studied model for human malignant hyperthermia (MH) susceptibility. Since involvement reactive oxygen species (ROS) mitochondria in MH crisis has been previously debated, here we sought to determine uptake its possible link with ROS production single isolated from flexor digitorum brevis...
Alternative splicing, the process by which exons within a pre-mRNA transcript are differentially joined or skipped, is crucial in skeletal muscle since it required both during myogenesis and post-natal life to reprogram transcripts of contractile proteins, metabolic enzymes, transcription factors functionally distinct fiber types. The importance such events underlined numerosity pathological conditions caused alternative splicing aberrations. Importantly, many Ca2+ homeostasis genes also...
Skeletal muscle, one of the most abundant tissue in body, is a highly regenerative tissue. Indeed, compared to other tissues that are not able regenerate after injury, skeletal muscle can fully upon mechanically, chemically, and infection-induced trauma. Several injury models have been developed thoroughly investigate physiological mechanisms regulating regeneration. This protocol describes how induce regeneration by taking advantage cardiotoxin (CTX)-induced model. The overall steps include...
ABSTRACT The Mitochondrial Ca 2+ Uniporter Channel (MCUC) allows calcium entry into the mitochondrial matrix to regulate energy metabolism but also cell death. Although, several MCUC components have been identified, molecular basis of signaling networks and their remodeling upon changes in uniporter activity not systematically assessed. Using an unbiased quantitative proteomic approach, we map interactome HEK293 cells under physiological conditions chronic loss or gain uptake. Besides all...