Function, Structure, and Biogenesis of Mitochondrial ATP Synthase

Ackerman, Sharon H.; Tzagoloff, Alexander

doi:10.1016/s0079-6603(05)80003-0

Cited by 108 publications

(106 citation statements)

References 154 publications

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“…Only trace amounts of fully assembled F 1 F O complexes were detected by BN-PAGE analysis in this mutant ( Fig.2A). The mutated Atp6p was synthesized efficiently (Fig.3) but failed to accumulate at the steady state (Fig.2B) indicating that it is rapidly eliminated from cells after synthesis [9,45]. Yeast Atp6p is typically degraded when it cannot assemble.…”

Section: Discussionmentioning

confidence: 99%

“…The ATP6 gene encodes ATP synthase subunit a, which is referred to as Atp6p in yeast. The ATP synthase (also called complex V) synthesizes ATP from ADP and inorganic phosphate using the energy of the electrochemical proton gradient established by the mitochondrial electron transport chain (complexes I-IV) [9]. Atp6p is a key subunit of the F O proton-translocating domain of the ATP synthase.…”

Section: Introductionmentioning

confidence: 99%

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Defining the impact on yeast ATP synthase of two pathogenic human mitochondrial DNA mutations, T9185C and T9191C

et al. 2014

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Mutations in the human mitochondrial ATP6 gene encoding ATP synthase subunit a/6 (referred to as Atp6p in yeast) are at the base of neurodegenerative disorders like Neuropathy Ataxia Retinitis Pigmentosa (NARP), Leigh syndrome (LS), Charcot-Marie-Tooth (CMT), and ataxia telangiectasia. In previous studies, using the yeast Saccharomyces cerevisiae as a model we were able to better define how several of these mutations impact the ATP synthase.Here we report the construction of yeast models of two other ATP6 pathogenic mutations, T9185C and T9191C. The first one was reported as conferring a mild, sometimes reversible, CMT clinical phenotype; the second one has been described in a patient presenting with severe LS. We found that an equivalent of the T9185C mutation partially impaired the functioning of yeast ATP synthase, with only a 30% deficit in mitochondrial ATP production.An equivalent of the mutation T9191C had much more severe effects, with a nearly complete block in yeast Atp6p assembly and an >95% drop in the rate of ATP synthesis. These findings provide a molecular basis for the relative severities of the diseases induced by T9185C and T9191C.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Defining the impact on yeast ATP synthase of two pathogenic human mitochondrial DNA mutations, T9185C and T9191C

et al. 2014

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“…Under homeostatic conditions, the proton gradient across the mitochondrial inner membrane forces protons from the intermembrane space, through the proton channel, and into the matrix; this proton movement coincides with a rotational change in the structure of the hydrophilic portion of the ATP synthase complex. When ADP and inorganic phosphate are available in the mitochondrial matrix, the series of conformational changes induced by proton movement (F 0 ) forces the F 1 pump to run in its reverse direction so that the catalytic substrates can bind to their appropriate sites and ATP can be released [2,4,5]. Disruption in the activity of the respiratory complexes of the ETC results not only in an energy deficit…”

Section: Mitochondrial Structure and Atp Synthesismentioning

confidence: 99%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

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“…In addition, these organelles are involved in the synthesis of amino acids, nucleotides, and lipids, in ion homeostasis and in cell proliferation, motility and programmed death [27][28][29]. The number, structure, and functions of mitochondria differ in animal cells and tissues in relation to the energetic needs [30,31], and in response to physiological or environmental alterations [32][33][34].…”

Section: Introductionmentioning

confidence: 99%