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Biochemistry (Moscow)

, Volume 83, Issue 2, pp 168–183 | Cite as

Myoglobin: Oxygen Depot or Oxygen Transporter to Mitochondria? A Novel Mechanism of Myoglobin Deoxygenation in Cells (review)

  • G. B. PostnikovaEmail author
  • E. A. Shekhovtsova
Hypothesis
  • 76 Downloads

Abstract

In this review, we shortly summarize the data of our studies (and also corresponding studies of other authors) on the new mechanism of myoglobin (Mb) deoxygenation in a cell, according to which Mb acts as an oxygen transporter, and its affinity for the ligand, like in other transporting proteins, is regulated by the interaction with the target, in our case, mitochondria (Mch). We firstly found that contrary to previously formulated and commonly accepted concepts, oxymyoglobin (MbO2) deoxygenation occurs only via interaction of the protein with respiring mitochondria (low \({p_{{O_2}}}\) values are necessary but not sufficient for this process to proceed). Detailed studies of the mechanism of Mb–Mch interaction by various physicochemical methods using natural and artificial bilayer phospholipid membranes showed that: (i) the rate of MbO2 deoxygenation in the presence of respiring Mch fully coincides with the rate of O2 uptake by mitochondria from a solution irrespectively of their state (native coupled, freshly frozen, or FCCP-uncoupled), i.e. it is determined by the respiratory activity of Mch; (ii) Mb nonspecifically binds to membrane phospholipids of the outer mitochondrial membrane, while any Mb-specific protein or phospholipid sites on it are lacking; (iii) oxygen uptake by Mch from a solution and the uptake of Mb-bound oxygen are two different processes, as their rates are differently affected by proteins (e.g. lysozyme) that compete with MbO2 for binding to the mitochondrial membrane; (iv) electrostatic forces significantly contribute to the Mb–membrane interactions; the dependence of these interactions on ionic strength is provided by the local electrostatic interactions between anionic groups of phospholipids (the heads) and invariant Lys and Arg residues near the Mb heme pocket; (v) interactions of Mb with phospholipid membranes promote conformational changes in the protein, primarily in its heme pocket, without significant alterations in the protein secondary and tertiary structures; and (vi) Mb–membrane interactions lead to decrease in the affinity of myoglobin for O2, which could be monitored by the increase in the MbO2 autooxidation rate under aerobic conditions and under anaerobic ones, by the shift in the MbO2/Mb(2) equilibrium towards the ligand-free protein. The decrease in the affinity of Mb for the ligand should facilitate O2 dissociation from MbO2 at physiological \({p_{{O_2}}}\) values in cells.

Keywords

myoglobin mitochondria spatial structure deoxygenation mechanism 

Abbreviation (biaoti)

apoMb

apomyoglobin

BLM

bilayer lipid membranes

BSA

bovine serum albumin

DMb

Mb diffusion coefficient

DPPG

1,2-dipalmitoylphosphatidylglycerol

FCCP

carbonylcyanide-4-(trifluoromethoxy)phenylhydrazone

GuHCl

guanidine chloride

Kdis

complex–ligand equilibrium dissociation constant

KM

Mb binding constant to mitochondria

kox

MbO2 autooxidation rate constant

M540

merocyanine 540

Mb

myoglobin

Mb(2)

deoxymyoglobin

MbO2

oxymyoglobin

Mch

mitochondria

metMb

metmyoglobin

\({p_{{O_2}}}\)

oxygen partial pressure

p50, \({p_{{O_2}}}\)

value at which Mb(2) is half-oxygenated (myoglobin affinity for oxygen)

POPG

1-palmitoyl-2-oleylglycero-3-phosphoglycerol

ROS

reactive oxygen species

\({S_{Mb{O_2}}}\)

extent of myoglobin saturation with oxygen.

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© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Institute of Cell BiophysicsRussian Academy of SciencesPushchino, Moscow RegionRussia

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