Malonyl‐CoA is a key intermediate in a number of metabolic processes associated with its role as a substrate in acylation and condensation reactions. These types of reactions occur in plastids, the cytosol and mitochondria, and although carboxylation of acetyl‐CoA is the known mechanism for generating the distinct plastidial and cytosolic pools, the metabolic origin of the mitochondrial malonyl‐CoA pool is still unclear. In this study we demonstrate that malonyl‐CoA synthetase encoded by the Arabidopsis
- Award ID(s):
- 1848057
- NSF-PAR ID:
- 10252373
- Editor(s):
- Beard, D
- Date Published:
- Journal Name:
- PLoS computational biology
- Volume:
- 17
- Issue:
- 6
- ISSN:
- 1553-7358
- Page Range / eLocation ID:
- e1009073
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Summary AAE 13AT 3G16170AAE 13 protein is not essential, due to the presence of a redundant malonyl‐CoA generating system provided by a cytosolic acetyl‐CoA carboxylase, the mitochondrialAAE 13 protein is essential for plant growth. Phenotypes of theaae13‐1 mutant are transgenically reversed only if the mitochondrial pre‐sequence is present in the ectopically expressedAAE 13 proteins. Theaae13‐1 mutant exhibits typical metabolic phenotypes associated with a deficiency in the mitochondrial fatty acid synthase system, namely depleted lipoylation of the H subunit of the photorespiratory enzyme glycine decarboxylase, increased accumulation of glycine and glycolate and reduced levels of sucrose. Most of these metabolic alterations, and associated morphological changes, are reversed when theaae13‐1 mutant is grown in a non‐photorespiratory condition (i.e. a 1%CO 2atmosphere), demonstrating that they are a consequence of the deficiency in photorespiration due to the inability to generate lipoic acid from mitochondrially synthesized fatty acids. -
null (Ed.)Tangential curvatures are a key geometric feature of tissue folds in the human cerebral cortex. In the brain, these smoother and firmer bends are called gyri and sulci and form distinctive curved tissue patterns imposing a mechanical stimulus on neuronal networks. This stimulus is hypothesized to be essential for proper brain cell function but lacks in most standard neuronal cell assays. A variety of soft lithographic micropatterning techniques can be used to integrate round geometries in cell assays. Most microfabricated patterns, however, focus only on a small set of defined curvatures. In contrast, curvatures in the brain span a wide physical range, leaving it unknown which precise role distinct curvatures may play on neuronal cell signaling. Here we report a hydrogel-based multi-curvature design consisting of over twenty bands of distinct parallel curvature ranges to precisely engineer neuronal networks' growth and signaling under patterns of arcs. Monitoring calcium and mitochondrial dynamics in primary rodent neurons grown over two weeks in the multi-curvature patterns, we found that static calcium signaling was locally attenuated under higher curvatures ( k > 0.01 μm −1 ). In contrast, to randomize growth, transient calcium signaling showed higher synchronicity when neurons formed networks in confined multi-curvature patterns. Additionally, we found that mitochondria showed lower motility under high curvatures ( k > 0.01 μm −1 ) than under lower curvatures ( k < 0.01 μm −1 ). Our results demonstrate how sensitive neuronal cell function may be linked and controlled through specific curved geometric features. Furthermore, the hydrogel-based multi-curvature design possesses high compatibility with various surfaces, allowing a flexible integration of geometric features into next-generation neuro devices, cell assays, tissue engineering, and implants.more » « less
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Abstract Intracellular organelles are membrane‐bound and biochemically distinct compartments constructed to serve specialized functions in eukaryotic cells. Through extensive interactions, they form networks to coordinate and integrate their specialized functions for cell physiology. A fundamental property of these organelle networks is that they constantly undergo dynamic organization via membrane fusion and fission to remodel their internal connections and to mediate direct material exchange between compartments. The dynamic organization not only enables them to serve critical physiological functions adaptively but also differentiates them from many other biological networks such as gene regulatory networks and cell signaling networks. This review examines this fundamental property of the organelle networks from a systems point of view. The focus is exclusively on homotypic networks formed by mitochondria, lysosomes, endosomes, and the endoplasmic reticulum, respectively. First, key mechanisms that drive the dynamic organization of these networks are summarized. Then, several distinct organizational properties of these networks are highlighted. Next, spatial properties of the dynamic organization of these networks are emphasized, and their functional implications are examined. Finally, some representative molecular machineries that mediate the dynamic organization of these networks are surveyed. Overall, the dynamic organization of intracellular organelle networks is emerging as a fundamental and unifying paradigm in the internal organization of eukaryotic cells.
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- Journal Article:
- https://doi.org/1009073
