The molecular machinery of Keilin's respiratory chain

2003 ◽  
Vol 31 (6) ◽  
pp. 1095-1105 ◽  
Author(s):  
P.R. Rich
Keyword(s):  
Respiratory Chain ◽  
Atp Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
New Era ◽  
Current State ◽  
Molecular Machinery ◽  
Tremendous Amount ◽  
Health And Disease ◽  
Level I ◽  
Prosthetic Groups

Keilin's classic paper of 1925 [Keilin (1925) Proc. R. Soc. London Ser. B 100, 129–151], achieved with simple, but elegant, techniques, describes the cytochrome components of the respiratory chain and their roles in intracellular respiration and oxygen consumption. Since that time, a tremendous amount of work has clarified the intricate details of the prosthetic groups, cofactors and proteins that comprise the respiratory chain and associated machinery for ATP synthesis. The work has culminated in advanced crystallographic and spectroscopic methods that provide structural and mechanistic details of this mitochondrial molecular machinery, in many instances to atomic level. I review here the current state of understanding of the mitochondrial respiratory chain in terms of structures and dynamics of the component proteins and their roles in the biological electron and proton transfer processes that result in ATP synthesis. These advances, together with emerging evidence of further diverse roles of mitochondria in health and disease, have prompted a new era of interest in mitochondrial function.

scholarly journals Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import

2010 ◽  
Vol 21 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Cristofol Vives-Bauza ◽  
Jordi Magrané ◽  
Antoni L. Andreu ◽  
Giovanni Manfredi
Keyword(s):  
Respiratory Chain ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Atp Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
Genetic Redundancy ◽  
Mitochondrial Protein Import ◽  
Atpase Subunit ◽  
Subunit C ◽  
And Function

In mammals, subunit c of the F1F0-ATP synthase has three isoforms (P1, P2, and P3). These isoforms differ by their cleavable mitochondrial targeting peptides, whereas the mature peptides are identical. To investigate this apparent genetic redundancy, we knocked down each of the three subunit c isoform by RNA interference in HeLa cells. Silencing any of the subunit c isoforms individually resulted in an ATP synthesis defect, indicating that these isoforms are not functionally redundant. We found that subunit c knockdown impaired the structure and function of the mitochondrial respiratory chain. In particular, P2 silencing caused defective cytochrome oxidase assembly and function. Because the expression of exogenous P1 or P2 was able to rescue the respective silencing phenotypes, but the two isoforms were unable to cross-complement, we hypothesized that their functional specificity resided in their targeting peptides. In fact, the expression of P1 and P2 targeting peptides fused to GFP variants rescued the ATP synthesis and respiratory chain defects in the silenced cells. Our results demonstrate that the subunit c isoforms are nonredundant, because they differ functionally by their targeting peptides, which, in addition to mediating mitochondrial protein import, play a yet undiscovered role in respiratory chain maintenance.

scholarly journals Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)

2018 ◽  
Vol 399 (11) ◽  
pp. 1249-1264 ◽  
Author(s):  
Tomoko Ohnishi ◽  
S. Tsuyoshi Ohnishi ◽  
John C. Salerno
Keyword(s):  
Electron Transfer ◽  
Respiratory Chain ◽  
Complex I ◽  
Proton Translocation ◽  
Atp Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
Proton Pumping ◽  
Entry Site ◽  
Quinone Oxidoreductase ◽  
Terminal Electron Acceptor

AbstractNADH-quinone oxidoreductase (complex I) is the largest and most complicated enzyme complex of the mitochondrial respiratory chain. It is the entry site into the respiratory chain for most of the reducing equivalents generated during metabolism, coupling electron transfer from NADH to quinone to proton translocation, which in turn drives ATP synthesis. Dysfunction of complex I is associated with neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and it is proposed to be involved in aging. Complex I has one non-covalently bound FMN, eight to 10 iron-sulfur clusters, and protein-associated quinone molecules as electron transport components. Electron paramagnetic resonance (EPR) has previously been the most informative technique, especially in membranein situanalysis. The structure of complex 1 has now been resolved from a number of species, but the mechanisms by which electron transfer is coupled to transmembrane proton pumping remains unresolved. Ubiquinone-10, the terminal electron acceptor of complex I, is detectable by EPR in its one electron reduced, semiquinone (SQ) state. In the aerobic steady state of respiration the semi-ubiquinone anion has been observed and studied in detail. Two distinct protein-associated fast and slow relaxing, SQ signals have been resolved which were designated SQNfand SQNs. This review covers a five decade personal journey through the field leading to a focus on the unresolved questions of the role of the SQ radicals and their possible part in proton pumping.

scholarly journals The mitochondrial respiratory chain is a modulator of apoptosis

2007 ◽  
Vol 179 (6) ◽  
pp. 1163-1177 ◽  
Author(s):  
Jennifer Q. Kwong ◽  
Matthew S. Henning ◽  
Anatoly A. Starkov ◽  
Giovanni Manfredi
Keyword(s):  
Er Stress ◽  
Respiratory Chain ◽  
Electron Flux ◽  
Atp Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
Dependent Manner ◽  
Atp Production ◽  
Dna Mutations ◽  
Increased Sensitivity ◽  
Induced Apoptosis

Mitochondrial dysfunction and dysregulation of apoptosis are implicated in many diseases such as cancer and neurodegeneration. We investigate here the role of respiratory chain (RC) dysfunction in apoptosis, using mitochondrial DNA mutations as genetic models. Although some mutations eliminate the entire RC, others target specific complexes, resulting in either decreased or complete loss of electron flux, which leads to impaired respiration and adenosine triphosphate (ATP) synthesis. Despite these similarities, significant differences in responses to apoptotic stimuli emerge. Cells lacking RC are protected against both mitochondrial- and endoplasmic reticulum (ER) stress–induced apoptosis. Cells with RC, but unable to generate electron flux, are protected against mitochondrial apoptosis, although they have increased sensitivity to ER stress. Finally, cells with a partial reduction in electron flux have increased apoptosis under both conditions. Our results show that the RC modulates apoptosis in a context-dependent manner independent of ATP production and that apoptotic responses are the result of the interplay between mitochondrial functional state and environmental cues.

scholarly journals Thermodynamic efficiency, reversibility, and degree of coupling in energy conservation by the mitochondrial respiratory chain

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Mårten Wikström ◽  
Roger Springett
Keyword(s):  
Respiratory Chain ◽  
Proton Translocation ◽  
Atp Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
Point Of View ◽  
Proton Gradient ◽  
Thermodynamic Efficiency ◽  
Inner Mitochondrial Membrane ◽  
Degree Of Coupling ◽  
Mitochondrial Respiratory

AbstractThe protonmotive mitochondrial respiratory chain, comprising complexes I, III and IV, transduces free energy of the electron transfer reactions to an electrochemical proton gradient across the inner mitochondrial membrane. This gradient is used to drive synthesis of ATP and ion and metabolite transport. The efficiency of energy conversion is of interest from a physiological point of view, since the energy transduction mechanisms differ fundamentally between the three complexes. Here, we have chosen actively phosphorylating mitochondria as the focus of analysis. For all three complexes we find that the thermodynamic efficiency is about 80–90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis. However, when net ATP synthesis stops at a high ATP/ADP.Pi ratio, and mitochondria reach “State 4” with an elevated proton gradient, the degree of coupling drops substantially. The mechanistic cause and the physiological implications of this effect are discussed.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

Sign in / Sign up

Export Citation Format

Share Document