scholarly journals AAA Proteases: Guardians of Mitochondrial Function and Homeostasis

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 163 ◽  
Author(s):  
Magdalena Opalińska ◽  
Hanna Jańska
Keyword(s):  
Adenosine Triphosphate ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Current Knowledge ◽  
Fine Tuning ◽  
Eukaryotic Cells ◽  
Mitochondrial Activity ◽  
Inner Mitochondrial Membrane ◽  
Membrane Bound ◽  
Aaa Atpases

Mitochondria are dynamic, semi-autonomous organelles that execute numerous life-sustaining tasks in eukaryotic cells. Functioning of mitochondria depends on the adequate action of versatile proteinaceous machineries. Fine-tuning of mitochondrial activity in response to cellular needs involves continuous remodeling of organellar proteome. This process not only includes modulation of various biogenetic pathways, but also the removal of superfluous proteins by adenosine triphosphate (ATP)-driven proteolytic machineries. Accordingly, all mitochondrial sub-compartments are under persistent surveillance of ATP-dependent proteases. Particularly important are highly conserved two inner mitochondrial membrane-bound metalloproteases known as m-AAA and i-AAA (ATPases associated with diverse cellular activities), whose mis-functioning may lead to impaired organellar function and consequently to development of severe diseases. Herein, we discuss the current knowledge of yeast, mammalian, and plant AAA proteases and their implications in mitochondrial function and homeostasis maintenance.

scholarly journals Genomic instability induced by radiation-mimicking chemicals is not associated with persistent mitochondrial degeneration

2021 ◽  
Author(s):  
Luukkonen Jukka ◽  
Höytö Anne ◽  
Sokka Miiko ◽  
Syväoja Juhani ◽  
Juutilainen Jukka ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ionizing Radiation ◽  
Genomic Instability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Neuroblastoma Cells ◽  
Superoxide Production ◽  
Mitochondrial Activity ◽  
Mitochondrial Superoxide

AbstractIonizing radiation has been shown to cause induced genomic instability (IGI), which is defined as a persistently increased rate of genomic damage in the progeny of the exposed cells. In this study, IGI was investigated by exposing human SH-SY5Y neuroblastoma cells to hydroxyurea and zeocin, two chemicals mimicking different DNA-damaging effects of ionizing radiation. The aim was to explore whether IGI was associated with persistent mitochondrial dysfunction. Changes to mitochondrial function were assessed by analyzing mitochondrial superoxide production, mitochondrial membrane potential, and mitochondrial activity. The formation of micronuclei was used to determine immediate genetic damage and IGI. Measurements were performed either immediately, 8 days, or 15 days following exposure. Both hydroxyurea and zeocin increased mitochondrial superoxide production and affected mitochondrial activity immediately after exposure, and mitochondrial membrane potential was affected by zeocin, but no persistent changes in mitochondrial function were observed. IGI became manifested 15 days after exposure in hydroxyurea-exposed cells. In conclusion, immediate responses in mitochondrial function did not cause persistent dysfunction of mitochondria, and this dysfunction was not required for IGI in human neuroblastoma cells.

scholarly journals The spatio-temporal dynamics of mitochondrial membrane potential during oocyte maturation

2019 ◽  
Vol 25 (11) ◽  
pp. 695-705 ◽  
Author(s):  
Usama AL-Zubaidi ◽  
Jun Liu ◽  
Ozgur Cinar ◽  
Rebecca L Robker ◽  
Deepak Adhikari ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Oocyte Maturation ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Local Level ◽  
Meiotic Spindle ◽  
Mitochondrial Activity ◽  
Wide Range ◽  
Spatio Temporal

Abstract Mitochondria are highly dynamic organelles and their distribution, structure and activity affect a wide range of cellular functions. Mitochondrial membrane potential (∆Ψm) is an indicator of mitochondrial activity and plays a major role in ATP production, redox balance, signaling and metabolism. Despite the absolute reliance of oocyte and early embryo development on mitochondrial function, there is little known about the spatial and temporal aspects of ΔΨm during oocyte maturation. The one exception is that previous findings using a ΔΨm indicator, JC-1, report that mitochondria in the cortex show a preferentially increased ΔΨm, relative to the rest of the cytoplasm. Using live-cell imaging and a new ratiometric approach for measuring ΔΨm in mouse oocytes, we find that ΔΨm increases through the time course of oocyte maturation and that mitochondria in the vicinity of the first meiotic spindle show an increase in ΔΨm, compared to other regions of the cytoplasm. We find no evidence for an elevated ΔΨm in the oocyte cortex. These findings suggest that mitochondrial activity is adaptive and responsive to the events of oocyte maturation at both a global and local level. In conclusion, we have provided a new approach to reliably measure ΔΨm that has shed new light onto the spatio-temporal regulation of mitochondrial function in oocytes and early embryos.

scholarly journals Molecular mechanism of mitochondrial phosphatidate transfer by Ups1

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jiuwei Lu ◽  
Chun Chan ◽  
Leiye Yu ◽  
Jun Fan ◽  
Fei Sun ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membranes ◽  
Inner Mitochondrial Membrane ◽  
Membrane Interaction ◽  
Detailed Mechanism ◽  
Physiological Regulator ◽  
Membrane Bound ◽  
Dynamics Simulations

AbstractCardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.

Two Forms of a Mitochondrial Endonuclease in Neurospora crassa

1975 ◽  
Vol 53 (7) ◽  
pp. 823-825 ◽  
Author(s):  
Charles E. Martin ◽  
Robert P. Wagner
Keyword(s):  
Molecular Weight ◽  
Neurospora Crassa ◽  
Mitochondrial Membrane ◽  
Nuclease Activity ◽  
Inner Mitochondrial Membrane ◽  
Detergent Treatment ◽  
Approximate Molecular Weight ◽  
Membrane Bound

Mitochondrial nuclease activity in Neurospora crassa occurs in membrane-bound and soluble forms in approximately equal proportions. These activities apparently are due to the same enzyme, which has an approximate molecular weight of 120 000. A portion of the insoluble enzyme appears to be associated with the inner mitochondrial membrane and is resistant to solubilization by detergent treatment as well as by physical disruption methods.

scholarly journals Improvement of bovine in vitro embryo production by vitamin K2 supplementation

Reproduction ◽  
2014 ◽  
Vol 148 (5) ◽  
pp. 489-497 ◽  
Author(s):  
Luis Manuel Baldoceda-Baldeon ◽  
Dominic Gagné ◽  
Christian Vigneault ◽  
Patrick Blondin ◽  
Claude Robert
Keyword(s):  
Vitamin K ◽  
Mitochondrial Function ◽  
Blastocyst Stage ◽  
Mitochondrial Activity ◽  
Bovine Embryos ◽  
Current Standard ◽  
Expression Of Genes ◽  
Mammalian Embryos ◽  
Membrane Bound

Mitochondria play an important role during early development in mammalian embryos. It has been shown that properly controlled follicular preparation increases the likelihood ofin-vitro-produced bovine embryos reaching the blastocyst stage and that competent embryos exhibit heightened expression of genes associated with mitochondrial function. We hypothesized that apparently incompetent embryos could be rescued by restoring mitochondrial function. It has been shown that vitamin K2(a membrane-bound electron carrier similar to ubiquinone) can restore mitochondrial dysfunction in eukaryotic cells. The aim of this study was therefore to investigate the effects of vitamin K2on bovine embryonic developmentin vitro. The vitamin was found most effective when added 72 h after fertilization. It produced a significant (P<0.05) increase in the percentage of blastocysts (+8.6%), more expanded blastocysts (+7.8%), and embryos of better morphological quality. It improved the mitochondrial activity significantly and had a measurable impact on gene expression. This is the first demonstration that current standard conditions ofin vitroproduction of bovine embryos may be inadequate due to the lack of support for mitochondrial function and may be improved significantly by supplementing the culture medium with vitamin K2.

scholarly journals Amyloid-Beta Interaction with Mitochondria

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lucia Pagani ◽  
Anne Eckert
Keyword(s):  
Mitochondrial Dysfunction ◽  
Amyloid Beta ◽  
Mitochondrial Membrane ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Intracellular Localization ◽  
Protein A ◽  
Postmortem Brain ◽  
Intermembrane Space ◽  
Inner Mitochondrial Membrane

Mitochondrial dysfunction is a hallmark of amyloid-beta(Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). The recent emphasis on the intracellular biology of Aβand its precursor protein (AβPP) has led researchers to consider the possibility that mitochondria-associated and/or intramitochondrial Aβmay directly cause neurotoxicity. In this paper, we will outline current knowledge of the intracellular localization of both Aβand AβPP addressing the question of how Aβcan access mitochondria. Moreover, we summarize evidence from AD postmortem brain as well as cellular and animal AD models showing that Aβtriggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species (ROS) production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. In particular, we focus on Aβinteraction with different mitochondrial targets including the outer mitochondrial membrane, intermembrane space, inner mitochondrial membrane, and the matrix. Thus, this paper establishes a modified model of the Alzheimer cascade mitochondrial hypothesis.

scholarly journals A Mutation in the Inner Mitochondrial Membrane Peptidase 2-Like Gene (Immp2l) Affects Mitochondrial Function and Impairs Fertility in Mice1

2008 ◽  
Vol 78 (4) ◽  
pp. 601-610 ◽  
Author(s):  
Baisong Lu ◽  
Christophe Poirier ◽  
Tamas Gaspar ◽  
Christian Gratzke ◽  
Wilbur Harrison ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Inner Mitochondrial Membrane

scholarly journals Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function

1998 ◽  
Vol 275 (5) ◽  
pp. H1567-H1576 ◽  
Author(s):  
Ekshon L. Holmuhamedov ◽  
Sofija Jovanović ◽  
Petras P. Dzeja ◽  
Aleksandar Jovanović ◽  
Andre Terzic
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Membrane Depolarization ◽  
Cardiac Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Induced Membrane ◽  
Channel Opener ◽  
Matrix Volume

Discovered in the cardiac sarcolemma, ATP-sensitive K+(KATP) channels have more recently also been identified within the inner mitochondrial membrane. Yet the consequences of mitochondrial KATP channel activation on mitochondrial function remain partially documented. Therefore, we isolated mitochondria from rat hearts and used K+ channel openers to examine the effect of mitochondrial KATPchannel opening on mitochondrial membrane potential, respiration, ATP generation, Ca2+ transport, and matrix volume. From a mitochondrial membrane potential of −180 ± 15 mV, K+ channel openers, pinacidil (100 μM), cromakalim (25 μM), and levcromakalim (20 μM), induced membrane depolarization by 10 ± 7, 25 ± 9, and 24 ± 10 mV, respectively. This effect was abolished by removal of extramitochondrial K+ or application of a KATP channel blocker. K+ channel opener-induced membrane depolarization was associated with an increase in the rate of mitochondrial respiration and a decrease in the rate of mitochondrial ATP synthesis. Furthermore, treatment with a K+ channel opener released Ca2+ from mitochondria preloaded with Ca2+, an effect also dependent on extramitochondrial K+concentration and sensitive to KATP channel blockade. In addition, K+ channel openers, cromakalim and pinacidil, increased matrix volume and released mitochondrial proteins, cytochrome cand adenylate kinase. Thus, in isolated cardiac mitochondria, KATP channel openers depolarized the membrane, accelerated respiration, slowed ATP production, released accumulated Ca2+, produced swelling, and stimulated efflux of intermembrane proteins. These observations provide direct evidence for a role of mitochondrial KATP channels in regulating functions vital for the cardiac mitochondria.

Sign in / Sign up

Export Citation Format

Share Document