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The body often responds to increased energy demands during growth or development by secreting thyroid hormone. Activated thyroid hormone receptors (TRs) increase long-term mitochondrial output through transcriptional changes. But on page 915, Saelim et al. show that some TRs supersede transcription to cause rapid, transient changes in mitochondrial function.
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The fast-acting TRs were those that were targeted to mitochondria rather than to the nucleus. Using frog oocytes, which lack their own TRs, the authors show that mitochondrial TRs energize respiration in response to thyroid hormone. These TRs did not require either their DNA-binding domains or transcriptional activities.8 ]1 U% y6 ^4 d$ U5 }1 a+ U
& K6 v" Z# B3 |. u' e& F$ i. l) tHow respiration was initially jump-started is not clear, but the mitochondria consumed more oxygen and had increased membrane potentials when mitochondrial TRs were activated. Presumably as a result of this increased potential, passive Ca2 uptake was stimulated, as seen by the ability of mitochondria to influence Ca2 release from the ER.
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A rapid, transient rise in mitochondrial respiration could serve several functions in the cell. First, the increase in mitochondrial Ca2 is likely to ramp up ATP production, as several enzymes in the citric acid cycle are Ca2 dependent. This might provide a temporary energy boost to tide cells over until the hormone's transcriptional effects lead to more mitochondria.
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$ m4 I1 J+ e. ]9 ^, B2 XSecond, increased mitochondrial Ca2 sequestration will reduce cytosolic Ca2 levels, thereby inhibiting Ca2 -dependent processes in the cytosol. Finally, the ability to activate rapidly the ability of mitochondria to take in Ca2 might be beneficial under conditions of cell stress or hypoxia. Stress-related cytoplasmic Ca2 spikes can have deleterious effects, including cell death. Limiting the damage caused by high Ca2 loads by the specific activation of mitochondrial TRs might be one way to curb neuronal death after a stroke.(Changes in calcium wave patterns show th) |
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发表于 2009-3-6 08:23
发表于 2015-5-24 20:41
