Contents

📒 Igamberdiev 2015

Optimization of ATP synthase function in mitochondria and chloroplasts via the adenylate kinase equilibrium1

Sciwheel.

INTRODUCTION

  • The reaction of ATP synthase: ADP + Mg + Pi + nH (ims) = MgATP + nH (mtx)
  • The optimal conditions of delivery of ADP and phosphate were analyzed in the concept of thermodynamic buffering via adenylate kinase (AK) and creatine kinase (CK) in the IMS.
    • AK : MgATP + AMP = MgADP + ADP
    • CK : ATP + Cr = ADP + CrP

BUFFERING OF PROTONS BY OTHER CATIONS IN ATP SYNTHESIS

  • there is not a very high difference in [H+] (ΔpH) between the matrix and the IMS of mitochondria
  • the concentration of Mg2+ ions in the IMS is close to mM (0.4mM)
  • the high concentration of K+, Mg2+, and other cations in the IMS represents a buffering mechanism preventing its drastic acidification
  • the futile ATP hydrolysis by the F1Fo complex is inhibited by the ATPase inhibitor protein (IF1), which is activated by low proton motive force (Δp)

THE ROLE OF MAGNESIUM IN THE MECHANISM OF ATP SYNTHESIS

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309032/bin/fpls-06-00010-g0001.jpg

  • F1Fo ATPase (ATP synthase): ADP + Mg2+ + Pi + nH (ims) = MgATP + nH (mtx)
    • Mg2+ acts as a separate substrate in the ATP synthase reaction, with profound catalytic effect
    • ATP synthesis is a spin-dependent ion-radical process (Mg-25 2-3x more effective than Mg-24 & Mg-26)
  • ANT: ATP(ims) + ADP(mtx) = ATP(mtx) + ADP(ims)
  • PiC (PT): H2PO4-(ims) + OH-(mtx) = H2PO4-(mtx) + OH-(ims)
  • Pi is a Mg2+ and Ca2+ buffer in the matrix
  • Ca2+ uptake by mitochondria via MCU is inhibited by Mg2+

EQUILIBRATION OF ADENYLATES OPTIMIZES ATP SYNTHESIS IN MITOCHONDRIA

  • AK acts as a thermodynamic buffer. adenylate concentration is adjusted to a correct value before being handed over by adenylate translocator (ANT), maintaining the linearity of oxidative phosphorylation within a physiological range
  • The futile equilibration of product with substrate may be considered as a price for the maintenance of the energy-efficient process. (via Apyrase: MgATP => AMP + PPi + Mg or MgADP => AMP + Pi + Mg)
  • Kcat of AK is 650 1/s which is one order of magnitude higher than that of ATP synthase and this is essential for efficient equilibration of substrate and product as in the case of other enzymes
  • AK provides the constant load of substrate (ADP) and Mg to ATP synthase
  • Concentrations of other ions (e.g., K+) are also adjusted via AK equilibrium
  • AMP as a signal, activating AMPK, enhance OXPHOS rates

TRANSPORT OF PHOSPHATE AND ADENYLATES IN MITOCHONDRIA

  • ANT : exchanges ADP and ATP, electrogenic (consumes one charge of ΔΨ)
  • PiC : Non-electrogenic, dependends on ΔpH (max flux > 10x of ATP synthesis rate)
  • Under the generation of a membrane potential, the gradient between free adenylate species is established according to the Nernst equation , and ATP free/ADP free ratio becomes lower inside and higher outside mitochondria
  • (In plants?) A very low [Mg2+] in the cytosol facilitates high ADP free/MgADP ratio, whereas in the matrix there is a very low ATP free/MgATP ratio. Cytosolic ADP has recently been postulated as the key factor controlling respiration, with [Mg2+] mediating not only free ADP level in cytosol, but also adenylate exchange across the IMM.
  • AK and mtCK are kept in the IMS to facilitate adenylates exchange and equilibrium

DYNAMIC ENVIRONMENT OF ATP SYNTHASE IN CHLOROPLASTS (omitted)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309032/bin/fpls-06-00010-g0002.jpg https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309032/bin/fpls-06-00010-g0003.jpg

NON-COUPLED PATHWAYS

“regulated uncoupling”

  • alternative oxidase (AOX) in the mitochondrial ETC in plants and fungi to oxidize excessive QH2
  • uncoupling proteins (UCPs) dissapates pmf
  • rotenone-insensitive NAD(P)H dehydrogenases (NDI1)
  • Provides strict regulatory control of concentrations of NADH/NAD+ and ATP/ADP

CONCLUSION

  • The steady fluxes of adenylates, magnesium, hydrogen ions and phosphate established via thermodynamic buffering and regulated uncoupling support optimal load and consumption of ATP synthase and provide its stable catalytic cycle
  • AK equilibrium represents an essential bioenergetic regulatory principle for the maintenance of steady regimes of ATP synthesis in mitochondria and chloroplasts (ratios of ATP and ADP, concentrations of Mg2+)

Other sources:

https://www.mdpi.com/ijms/ijms-10-01729/article_deploy/html/images/ijms-10-01729f1.png
AK shuttle (twice as efficient than ADP alone)

References


  1. Igamberdiev AU, Kleczkowski LA. Optimization of ATP synthase function in mitochondria and chloroplasts via the adenylate kinase equilibrium. Front. Plant Sci. 2015;6:10. doi:10.3389/fpls.2015.00010. PMC4309032↩︎