Mitochondrial cristae narrowing upon higher 2-oxoglutarate load

Dlasková, Andrea; Špaček, Tomáš; Engstová, Hana; Špačková, Jitka; Schröfel, Adam; Holendová, Blanka; Smolková, Katarína; Plecitá–Hlavatá, Lydie; Ježek, Petr

doi:10.1016/j.bbabio.2019.06.015

Cited by 34 publications

(57 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Fig. 1, a mitochondrial crista may be considered as an ellipsoidal-shaped 3D-structure [66][67][68][69] which can be described by a tri-axial (a, b, and c) ellipsoid equation (Eq. 12) in 3-dimensional x, y, and z coordinates.…”

Section: Resultsmentioning

confidence: 99%

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

Lee

2020

Sci Rep

View full text Add to dashboard Cite

Lee for decades, it was not entirely clear why mitochondria develop cristae? the work employing the transmembrane-electrostatic proton localization theory reported here has now provided a clear answer to this fundamental question. Surprisingly, the transmembrane-electrostatically localized proton concentration at a curved mitochondrial crista tip can be significantly higher than that at the relatively flat membrane plane regions where the proton-pumping respiratory supercomplexes are situated. The biological significance for mitochondrial cristae has now, for the first time, been elucidated at a protonic bioenergetics level: 1) The formation of cristae creates more mitochondrial inner membrane surface area and thus more protonic capacitance for transmembrane-electrostatically localized proton energy storage; and 2) The geometric effect of a mitochondrial crista enhances the transmembraneelectrostatically localized proton density to the crista tip where the Atp synthase can readily utilize the localized proton density to drive ATP synthesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

Lee

2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…As a result, cristae have traditionally been thought of as stable structures despite the widespread observations of individual mitochondria as dynamic structures over the past two decades (Nunnari et al, 1997;Bleazard et al, 1999;Karbowski et al, 2004;Szabadkai et al, 2004;Twig et al, 2008b;Molina et al, 2009;Lewis et al, 2016). However, recent technological advances have brought the resolution of the light microscope down into the tens of nanometer range which has finally permitted observation of cristae structures in live cells (Dlasková et al, 2018(Dlasková et al, , 2019Ježek and Dlasková, 2019;Jakobs et al, 2020; Figure 1 bottom left). Application of these super-resolution microscopy techniques to mitochondria from several types of cell culture systems have indeed revealed that cristae are dynamic structures capable of both fission and fusion-type events similar to those which occur at the organelle level (Huang et al, 2018;Stephan et al, 2019;Wang et al, 2019).…”

Section: Cristae Dynamicsmentioning

confidence: 99%

The Functional Impact of Mitochondrial Structure Across Subcellular Scales

et al. 2020

View full text Add to dashboard Cite

Mitochondria are key determinants of cellular health. However, the functional role of mitochondria varies from cell to cell depending on the relative demands for energy distribution, metabolite biosynthesis, and/or signaling. In order to support the specific needs of different cell types, mitochondrial functional capacity can be optimized in part by modulating mitochondrial structure across several different spatial scales. Here we discuss the functional implications of altering mitochondrial structure with an emphasis on the physiological trade-offs associated with different mitochondrial configurations. Within a mitochondrion, increasing the amount of cristae in the inner membrane improves capacity for energy conversion and free radical-mediated signaling but may come at the expense of matrix space where enzymes critical for metabolite biosynthesis and signaling reside. Electrically isolating individual cristae could provide a protective mechanism to limit the spread of dysfunction within a mitochondrion but may also slow the response time to an increase in cellular energy demand. For individual mitochondria, those with relatively greater surface areas can facilitate interactions with the cytosol or other organelles but may be more costly to remove through mitophagy due to the need for larger phagophore membranes. At the network scale, a large, stable mitochondrial reticulum can provide a structural pathway for energy distribution and communication across long distances yet also enable rapid spreading of localized dysfunction. Highly dynamic mitochondrial networks allow for frequent content mixing and communication but require constant cellular remodeling to accommodate the movement of mitochondria. The formation of contact sites between mitochondria and several other organelles provides a mechanism for specialized communication and direct content transfer between organelles. However, increasing the number of contact sites between mitochondria and any given organelle reduces the mitochondrial surface area available for contact sites with other organelles as well as for metabolite exchange with cytosol. Though the precise mechanisms guiding the coordinated multi-scale mitochondrial configurations observed in different cell types have yet to be elucidated, it is clear that mitochondrial structure is tailored at every level to optimize mitochondrial function to meet specific cellular demands.

show abstract

“…Recently, it was shown that CJs provide electric insulation between cristae that can display different membrane potential (Wolf et al, 2019). Cristae shape varies considerably depending on the bioenergetic demands during physiological changes and stress, including hypoxia, nutrient starvation, ROS, or induction of apoptosis (Mannella, 2006;Gomes et al, 2011;Cogliati et al, 2016;Pernas & Scorrano, 2016;Plecita-Hlavata et al, 2016;Baker et al, 2019;Dlaskova et al, 2019). The shape of cristae was suggested to govern the assembly and the stability of the respiratory chain complexes (RCs) and supercomplexes (SCs) (Cogliati et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes

et al. 2020

View full text Add to dashboard Cite

Homologous apolipoproteins of MICOS complex, MIC26 and MIC27, show an antagonistic regulation of their protein levels, making it difficult to deduce their individual functions using a single gene deletion. We obtained single and double knockout (DKO) human cells of MIC26 and MIC27 and found that DKO show more concentric onion-like cristae with loss of CJs than any single deletion indicating overlapping roles in formation of CJs. Using a combination of complexome profiling, STED nanoscopy, and blue-native gel electrophoresis, we found that MIC26 and MIC27 are dispensable for the stability and integration of the remaining MICOS subunits into the complex suggesting that they assemble late into the MICOS complex. MIC26 and MIC27 are cooperatively required for the integrity of respiratory chain (super) complexes (RCs/SC) and the F1Fo–ATP synthase complex and integration of F1 subunits into the monomeric F1Fo–ATP synthase. While cardiolipin was reduced in DKO cells, overexpression of cardiolipin synthase in DKO restores the stability of RCs/SC. Overall, we propose that MIC26 and MIC27 are cooperatively required for global integrity and stability of multimeric OXPHOS complexes by modulating cardiolipin levels.

show abstract

Mitochondrial cristae narrowing upon higher 2-oxoglutarate load

Cited by 34 publications

References 58 publications

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

The Functional Impact of Mitochondrial Structure Across Subcellular Scales

MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes

Contact Info

Product

Resources

About