Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Metabolite gradients might guide mitochondrial localization in cells and angiogenesis in tissues. It is unclear whether they can exist in single cells, because the length scale of most cells is small compared to the expected diffusion times of metabolites. For investigation of metabolic gradients, we need experimental systems in which spatial patterns of metabolism can be systematically measured and manipulated. We used concentrated cytoplasmic extracts from Xenopus eggs as a model cytoplasm, and visualized metabolic gradients formed in response to spatial stimuli. Restriction of oxygen supply to the edge of a drop mimicked distance to the surface of a single cell, or distance from a blood vessel in tissue. We imaged a step-like increase of Nicotinamide adenine dinucleotide (NAD) reduction approximately 600 microm distant from the oxygen source. This oxic-anoxic switch was preceded on the oxic side by a gradual rise of mitochondrial transmembrane potential (Deltapsi) and reactive oxygen species (ROS) production, extending over approximately 600 microm and approximately 300 microm, respectively. Addition of Adenosine triphosphate (ATP)-consuming beads mimicked local energy sinks in the cell. We imaged Deltapsi gradients with a decay length of approximately 50-300 microm around these beads, in the first visualization of an energy demand signaling gradient. Our study demonstrates that mitochondria can pattern the cytoplasm over length scales that are suited to convey morphogenetic information in large cells and tissues and provides a versatile model system for probing of the formation and function of metabolic gradients.
Bell,
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production.
2007, Pubmed
Bell,
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production.
2007,
Pubmed Chance,
Mitochondrial NADH redox state, monitoring discovery and deployment in tissue.
2004,
Pubmed Chance,
Optical method.
1991,
Pubmed de Graaf,
In vivo (31)P-NMR diffusion spectroscopy of ATP and phosphocreatine in rat skeletal muscle.
2000,
Pubmed Desai,
The use of Xenopus egg extracts to study mitotic spindle assembly and function in vitro.
1999,
Pubmed
,
Xenbase Dworkin,
Metabolic regulation during early frog development: glycogenic flux in Xenopus oocytes, eggs, and embryos.
1989,
Pubmed
,
Xenbase Guzy,
Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia.
2006,
Pubmed Helmlinger,
Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation.
1997,
Pubmed Hickey,
Regulation of angiogenesis by hypoxia and hypoxia-inducible factors.
2006,
Pubmed Hochachka,
Cellular metabolic homeostasis during large-scale change in ATP turnover rates in muscles.
1997,
Pubmed Hollenbeck,
The axonal transport of mitochondria.
2005,
Pubmed Jacobus,
Theoretical support for the heart phosphocreatine energy transport shuttle based on the intracellular diffusion limited mobility of ADP.
1985,
Pubmed Jones,
Intracellular diffusion gradients of O2 and ATP.
1986,
Pubmed Krogh,
The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue.
1919,
Pubmed Kushmerick,
Ionic mobility in muscle cells.
1969,
Pubmed Misra,
The univalent reduction of oxygen by reduced flavins and quinones.
1972,
Pubmed Pelicano,
Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism.
2006,
Pubmed Rumsey,
Oxygen pressure distribution in the heart in vivo and evaluation of the ischemic "border zone".
1994,
Pubmed Rumsey,
Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat.
1990,
Pubmed Song,
OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L.
2007,
Pubmed Steenbergen,
Heterogeneity of the hypoxic state in perfused rat heart.
1977,
Pubmed Vendelin,
Regulation of mitochondrial respiration in heart cells analyzed by reaction-diffusion model of energy transfer.
2000,
Pubmed
