ArticleBiochimica et biophysica acta2015
Critical determinants of mitochondria-associated neutral sphingomyelinase (MA-nSMase) for mitochondrial localization.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Purification and Characterization of Mitochondrial MgMolecules and cells · 2023Article
- Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate.Antioxidants (Basel, Switzerland) · 2023Review
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- RanGTPase links nucleo-cytoplasmic transport to the recruitment of cargoes into small extracellular vesicles.Cellular and molecular life sciences : CMLS · 2022Article
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases.Journal of lipid research · 2019Article
- Approaches for probing and evaluating mammalian sphingolipid metabolism.Analytical biochemistry · 2019Review
- Sphingolipids as Emerging Mediators in Retina Degeneration.Frontiers in cellular neuroscience · 2019Review
- Visualizing bioactive ceramides.Chemistry and physics of lipids · 2018Review
- Sphingolipids and lipid rafts: Novel concepts and methods of analysis.Chemistry and physics of lipids · 2018Review
- Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018Review
- Sphingolipids in mitochondria.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- Lactosylceramide contributes to mitochondrial dysfunction in diabetes.Journal of lipid research · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundA novel murine mitochondria-associated neutral sphingomyelinase (MA-nSMase) has been recently cloned and partially characterized. The subcellular localization of the enzyme was found to be predominant in mitochondria. In this work, the determinants of mitochondrial localization and its topology were investigated.
methodsMA-nSMase mutants lacking consecutive regions and fusion proteins of GFP with truncated MA-nSMase regions were constructed and expressed in MCF-7 cells. Its localization was analyzed using confocal microscopy and sub-cellular fractionation methods. The sub-mitochondrial localization of MA-nSMase was determined using protease protection assay on isolated mitochondria.
resultsThe results initially showed that a putative mitochondrial localization signal (MLS), homologous to an MLS in the zebra-fish mitochondrial SMase is not necessary for the mitochondrial localization of the murine MA-nSMase. Evidence is provided to the presence of two regions in MA-nSMase that are sufficient for mitochondrial localization: a signal sequence (amino acids 24-56) that is responsible for the mitochondrial localization and an additional 'signal-anchor' sequence (amino acids 77-99) that anchors the protein to the mitochondrial membrane. This protein is topologically located in the outer mitochondrial membrane where both the C and N-termini remain exposed to the cytosol.
conclusionsMA-nSMase is a membrane anchored protein with a MLS and a signal-anchor sequence at its N-terminal to localize it to the outer mitochondrial membrane. GENERAL SIGNIFICANCE: Mitochondrial sphingolipids have been reported to play a critical role in cellular viability. This study opens a new window to investigate their cellular functions, and to define novel therapeutic targets.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.