Pathway Human Homo sapiens

Respiratory electron transport

R-HSA-611105 in Reactome release 97: under Aerobic respiration and respiratory electron transport, with 159 genes placed in it by the mapping files and 4 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-611105 (mouse), R-RNO-611105 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-611105.8
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2009-12-15
Last updated: 2021-03-24
Events inside: 11, counted from the record

Mitochondria are often described as the "powerhouse" of a cell as it is here that energy is largely released from the oxidation of food. Reducing equivalents generated from beta-oxidation of fatty acids and from the Krebs cycle enter the electron transport chain (also called the respiratory chain). During a series of redox reactions, electrons travel down the chain releasing their energy in controlled steps. These reactions drive the active transport of protons from the mitochondrial matrix , through the inner membrane to the intermembrane space. The respiratory chain consists of five main types of carrier; flavins, iron-sulfur centres, quinones, cytochromes (heme proteins) and copper. The two main reducing equivalents entering the respiratory chain are NADH and FADH2. NADH is linked through the NADH-specific dehydrogenase whereas FADH2 is reoxidised within succinate dehydrogenase and a ubiquinone reductase of the fatty acid oxidation pathway. Oxygen is the final acceptor of electrons and with protons, is converted to form water, the end product of aerobic cellular respiration. A proton electrochemical gradient (often called protonmotive force) is established across the inner membrane, with positive charge in the intermembrane space relative to the matrix. Protons driven by the proton-motive force, can enter ATP synthase thus returning to the mitochondrial matrix. ATP synthases use this exergonic flow to form ATP in the matrix, a process called chemiosmotic coupling. A by-product of this process is heat generation.

An antiport, ATP-ADP translocase, preferentially exports ATP from the matrix thereby maintaining a high ADP:ATP ratio in the matrix. The tight coupling of electron flow to ATP synthesis means oxygen consumption is dependent on ADP availability (termed respiratory control). High ADP (low ATP) increases electron flow thereby increasing oxygen consumption and low ADP (high ATP) decreases electron flow and thereby decreases oxygen consumption. There are many inhibitors of mitochondrial ATP synthesis. Most act by either blocking the flow of electrons (eg cyanide, carbon monoxide, rotenone) or uncoupling electron flow from ATP synthesis (eg dinitrophenol). Thermogenin is a natural protein found in brown fat. Newborn babies have a large amount of brown fat and the heat generated by thermogenin is an alternative to ATP synthesis (and thus electron flow only produces heat) and allows the maintenance of body temperature in newborns.

The electron transport chain is located in the inner mitochondrial membrane and comprises some 80 proteins organized in four enzymatic complexes (I-IV). Complex V generates ATP but has no electron transfer activity. In addition to these 5 complexes, there are also two electron shuttle molecules; Coenzyme Q (also known as ubiquinone, CoQ) and Cytochrome c (Cytc). These two molecules shuttle electrons between the large complexes in the chain.

How many ATPs are generated by this process? Theoretically, for each glucose molecule, 32 ATPs can be produced. As electrons drop from NADH to oxygen in the chain, the number of protons pumped out and returning through ATP synthase can produce 2.5 ATPs per electron pair. For each pair donated by FADH2, only 1.5 ATPs can be formed. Twelve pairs of electrons are removed from each glucose molecule;

10 by NAD+ = 25 ATPs

2 by FADH2 = 3 ATPs.

Making a total of 28 ATPs. However, 2 ATPs are formed during the Krebs' cycle and 2 ATPs formed during glycolysis for each glucose molecule therefore making a total ATP yield of 32 ATPs. In reality, the energy from the respiratory chain is used for other processes (such as active transport of important ions and molecules) so under conditions of normal respiration, the actual ATP yield probably does not reach 32 ATPs.

The reducing equivalents that fuel the electron transport chain, namely NADH and FADH2, are produced by the Krebs cycle (TCA cycle) and the beta-oxidation of fatty acids. At three steps in the Krebs cycle (isocitrate conversion to oxoglutarate; oxoglutarate conversion to succinyl-CoA; Malate conversion to oxaloacetate), a pair of electrons (2e-) are removed and transferred to NAD+, forming NADH and H+. At a single step, a pair of electrons are removed from succinate, reducing FAD to FADH2. From the beta-oxidation of fatty acids, one step in the process forms NADH and H+ and another step forms FADH2.

Cytoplasmic NADH, generated from glycolysis, has to be oxidized to reform NAD+, essential for glycolysis, otherwise glycolysis would cease to function. There is no carrier that transports NADH directly into the mitochondrial matrix and the inner mitochondrial membrane is impermeable to NADH so the cell uses two shuttle systems to move reducing equivalents into the mitochondrion and regenerate cytosolic NAD+.

The first is the glycerol phosphate shuttle, which uses electrons from cytosolic NADH to produce FADH2 within the inner membrane. These electrons then flow to Coenzyme Q. Complex I is bypassed so only 1.5 ATPs can be formed per NADH via this route. The overall balanced equation, summing all the reactions in this system, is

NADH (cytosol) + H+ (cytosol) + NAD+ (mito.) = NAD+ (cytosol) + NADH (mito.) + H+ (mito.)

The malate-aspartate shuttle uses the oxidation of malate to generate NADH in the mitochondrial matrix. This NADH can then be fed directly to complex I and thus can form 3 ATPs via the respiratory chain. The overall balanced equation is

NADH (cytosol) + H+ (cytosol) + FAD (inner memb.) = NAD+ (cytosol) + FADH2 (inner memb.)

Both of these shuttle systems regenerate cytosolic NAD+.

The entry point for NADH is complex I (NADH dehydrogenase) and the entry point for FADH2 is Coenzyme Q. The input of electrons from fatty acid oxidation via ubiquinone is complicated and not shown in the diagram.

Literature Reactome attaches

The mitochondrial electron transport and oxidative phosphorylation systemAnnu Rev Biochem, 1985, vol. 54, p. 1015-69PubMed 2862839
Biochemical Pathways - An Atlas of Biochemistry and Molecular Biology1999, p. 193-200
Biochemistry - The Chemical Reactions of Living Cells 2nd Edn.2003, p. 1018-84
Harper's Biochemistry 25th ed1999, p. 137-48
Lehninger - Principles of Biochemistry 4th ed2005, p. 690-750
Bioenergetics 21992, p. 107-156
Still a puzzle: why is haem covalently attached in c-type cytochromes?Structure Fold Des, 1999, vol. 7, p. R281-90PubMed 10647174

Reactome's record lists 14 orthologous events, R-RNO-611105 (Rattus norvegicus), R-MMU-611105 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-05 ET · Reactome pathway browser"Respiratory electron transport". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-611105 with StableID: R-HSA-611105.8 (accessed 2026-10-05 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 159 genes in this human pathway; showing 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneACAD9	AuthorityHGNC:21497	Mapping file id28976 NCBI file	EvidenceTAS
GeneBCS1L	AuthorityHGNC:1020	Mapping file id617 NCBI file	EvidenceIEA
GeneCMC1	AuthorityHGNC:28783	Mapping file id152100 NCBI file	EvidenceTAS
GeneCOA1	AuthorityHGNC:21868	Mapping file id55744 NCBI file	EvidenceTAS
GeneCOA3	AuthorityHGNC:24990	Mapping file id28958 NCBI file	EvidenceTAS
GeneCOA5	AuthorityHGNC:33848	Mapping file id493753 NCBI file	EvidenceTAS
GeneCOQ10A	AuthorityHGNC:26515	Mapping file id93058 NCBI file	EvidenceTAS
GeneCOQ10B	AuthorityHGNC:25819	Mapping file id80219 NCBI file	EvidenceTAS
GeneCOX11	AuthorityHGNC:2261	Mapping file id1353 NCBI file	EvidenceTAS
GeneCOX14	AuthorityHGNC:28216	Mapping file id84987 NCBI file	EvidenceTAS
GeneCOX15	AuthorityHGNC:2263	Mapping file id1355 NCBI file	EvidenceTAS
GeneCOX16	AuthorityHGNC:20213	Mapping file id51241 NCBI file	EvidenceTAS
GeneCOX17	AuthorityHGNC:2264	Mapping file id10063 NCBI file	EvidenceTAS
GeneCOX18	AuthorityHGNC:26801	Mapping file id285521 NCBI file	EvidenceTAS
GeneCOX19	AuthorityHGNC:28074	Mapping file id90639 NCBI file	EvidenceTAS
GeneCOX20	AuthorityHGNC:26970	Mapping file id116228 NCBI file	EvidenceTAS
GeneCOX4I1	AuthorityHGNC:2265	Mapping file id1327 NCBI file	EvidenceTAS
GeneCOX4I2	AuthorityHGNC:16232	Mapping file id84701 NCBI file	EvidenceTAS
GeneCOX5A	AuthorityHGNC:2267	Mapping file id9377 NCBI file	EvidenceTAS
GeneCOX5B	AuthorityHGNC:2269	Mapping file id1329 NCBI file	EvidenceTAS
GeneCOX6A1	AuthorityHGNC:2277	Mapping file id1337 NCBI file	EvidenceTAS
GeneCOX6A2	AuthorityHGNC:2279	Mapping file id1339 NCBI file	EvidenceTAS
GeneCOX6B1	AuthorityHGNC:2280	Mapping file id1340 NCBI file	EvidenceTAS
GeneCOX6B2	AuthorityHGNC:24380	Mapping file id125965 NCBI file	EvidenceTAS
GeneCOX6C	AuthorityHGNC:2285	Mapping file id1345 NCBI file	EvidenceTAS
GeneCOX7A1	AuthorityHGNC:2287	Mapping file id1346 NCBI file	EvidenceTAS
GeneCOX7A2	AuthorityHGNC:2288	Mapping file id1347 NCBI file	EvidenceTAS
GeneCOX7A2L	AuthorityHGNC:2289	Mapping file id9167 NCBI file	EvidenceTAS
GeneCOX7B	AuthorityHGNC:2291	Mapping file id1349 NCBI file	EvidenceTAS
GeneCOX7C	AuthorityHGNC:2292	Mapping file id1350 NCBI file	EvidenceTAS
GeneCOX8A	AuthorityHGNC:2294	Mapping file id1351 NCBI file	EvidenceTAS
GeneCOX8C	AuthorityHGNC:24382	Mapping file id341947 NCBI file	EvidenceTAS
GeneCOXFA4	AuthorityHGNC:7687	Mapping file id4697 NCBI file	EvidenceTAS
GeneCYC1	AuthorityHGNC:2579	Mapping file id1537 NCBI file	EvidenceIEA, TAS
GeneCYCS	AuthorityHGNC:19986	Mapping file id54205 NCBI file	EvidenceTAS
GeneDMAC1	AuthorityHGNC:30536	Mapping file id90871 NCBI file	EvidenceTAS
GeneDMAC2	AuthorityHGNC:25496	Mapping file id55101 NCBI file	EvidenceTAS
GeneECSIT	AuthorityHGNC:29548	Mapping file id51295 NCBI file	EvidenceTAS
GeneETFA	AuthorityHGNC:3481	Mapping file id2108 NCBI file	EvidenceTAS
GeneETFB	AuthorityHGNC:3482	Mapping file id2109 NCBI file	EvidenceTAS
GeneETFDH	AuthorityHGNC:3483	Mapping file id2110 NCBI file	EvidenceTAS
GeneFOXRED1	AuthorityHGNC:26927	Mapping file id55572 NCBI file	EvidenceTAS
GeneFXN	AuthorityHGNC:3951	Mapping file id2395 NCBI file	EvidenceTAS
GeneGOT1	AuthorityHGNC:4432	Mapping file id2805 NCBI file	EvidenceTAS
GeneGOT2	AuthorityHGNC:4433	Mapping file id2806 NCBI file	EvidenceTAS
GeneHCCS	AuthorityHGNC:4837	Mapping file id3052 NCBI file	EvidenceTAS
GeneHIGD1A	AuthorityHGNC:29527	Mapping file id25994 NCBI file	EvidenceTAS
GeneHIGD1C	AuthorityHGNC:28044	Mapping file id613227 NCBI file	EvidenceTAS
GeneHIGD2A	AuthorityHGNC:28311	Mapping file id192286 NCBI file	EvidenceTAS
GeneHSCB	AuthorityHGNC:28913	Mapping file id150274 NCBI file	EvidenceTAS
GeneHSPA9	AuthorityHGNC:5244	Mapping file id3313 NCBI file	EvidenceTAS
GeneISCU	AuthorityHGNC:29882	Mapping file id23479 NCBI file	EvidenceTAS
GeneLETM1	AuthorityHGNC:6556	Mapping file id3954 NCBI file	EvidenceIEA
GeneLYRM2	AuthorityHGNC:25229	Mapping file id57226 NCBI file	EvidenceTAS
GeneLYRM4	AuthorityHGNC:21365	Mapping file id57128 NCBI file	EvidenceTAS
GeneLYRM7	AuthorityHGNC:28072	Mapping file id90624 NCBI file	EvidenceTAS
GeneMDH1	AuthorityHGNC:6970	Mapping file id4190 NCBI file	EvidenceTAS
GeneMDH2	AuthorityHGNC:6971	Mapping file id4191 NCBI file	EvidenceTAS
GeneMT-CO1	AuthorityHGNC:7419	Mapping file id4512 NCBI file	EvidenceTAS
GeneMT-CO2	AuthorityHGNC:7421	Mapping file id4513 NCBI file	EvidenceTAS
GeneMT-CO3	AuthorityHGNC:7422	Mapping file id4514 NCBI file	EvidenceTAS
GeneMT-CYB	AuthorityHGNC:7427	Mapping file id4519 NCBI file	EvidenceIEA, TAS
GeneMT-ND1	AuthorityHGNC:7455	Mapping file id4535 NCBI file	EvidenceTAS
GeneMT-ND2	AuthorityHGNC:7456	Mapping file id4536 NCBI file	EvidenceTAS
GeneMT-ND3	AuthorityHGNC:7458	Mapping file id4537 NCBI file	EvidenceTAS
GeneMT-ND4	AuthorityHGNC:7459	Mapping file id4538 NCBI file	EvidenceTAS
GeneMT-ND5	AuthorityHGNC:7461	Mapping file id4540 NCBI file	EvidenceTAS
GeneMT-ND6	AuthorityHGNC:7462	Mapping file id4541 NCBI file	EvidenceTAS
GeneNDUFA1	AuthorityHGNC:7683	Mapping file id4694 NCBI file	EvidenceTAS
GeneNDUFA10	AuthorityHGNC:7684	Mapping file id4705 NCBI file	EvidenceTAS
GeneNDUFA11	AuthorityHGNC:20371	Mapping file id126328 NCBI file	EvidenceTAS
GeneNDUFA12	AuthorityHGNC:23987	Mapping file id55967 NCBI file	EvidenceTAS
GeneNDUFA13	AuthorityHGNC:17194	Mapping file id51079 NCBI file	EvidenceTAS
GeneNDUFA2	AuthorityHGNC:7685	Mapping file id4695 NCBI file	EvidenceTAS
GeneNDUFA3	AuthorityHGNC:7686	Mapping file id4696 NCBI file	EvidenceTAS
GeneNDUFA5	AuthorityHGNC:7688	Mapping file id4698 NCBI file	EvidenceTAS
GeneNDUFA6	AuthorityHGNC:7690	Mapping file id4700 NCBI file	EvidenceTAS
GeneNDUFA7	AuthorityHGNC:7691	Mapping file id4701 NCBI file	EvidenceTAS
GeneNDUFA8	AuthorityHGNC:7692	Mapping file id4702 NCBI file	EvidenceTAS
GeneNDUFA9	AuthorityHGNC:7693	Mapping file id4704 NCBI file	EvidenceTAS
GeneNDUFAB1	AuthorityHGNC:7694	Mapping file id4706 NCBI file	EvidenceTAS
GeneNDUFAF1	AuthorityHGNC:18828	Mapping file id51103 NCBI file	EvidenceTAS
GeneNDUFAF2	AuthorityHGNC:28086	Mapping file id91942 NCBI file	EvidenceTAS
GeneNDUFAF3	AuthorityHGNC:29918	Mapping file id25915 NCBI file	EvidenceTAS
GeneNDUFAF4	AuthorityHGNC:21034	Mapping file id29078 NCBI file	EvidenceTAS
GeneNDUFAF5	AuthorityHGNC:15899	Mapping file id79133 NCBI file	EvidenceTAS
GeneNDUFAF6	AuthorityHGNC:28625	Mapping file id137682 NCBI file	EvidenceTAS
GeneNDUFAF7	AuthorityHGNC:28816	Mapping file id55471 NCBI file	EvidenceTAS
GeneNDUFAF8	AuthorityHGNC:33551	Mapping file id284184 NCBI file	EvidenceTAS
GeneNDUFB1	AuthorityHGNC:7695	Mapping file id4707 NCBI file	EvidenceTAS
GeneNDUFB10	AuthorityHGNC:7696	Mapping file id4716 NCBI file	EvidenceTAS
GeneNDUFB11	AuthorityHGNC:20372	Mapping file id54539 NCBI file	EvidenceTAS
GeneNDUFB2	AuthorityHGNC:7697	Mapping file id4708 NCBI file	EvidenceTAS
GeneNDUFB3	AuthorityHGNC:7698	Mapping file id4709 NCBI file	EvidenceTAS
GeneNDUFB4	AuthorityHGNC:7699	Mapping file id4710 NCBI file	EvidenceTAS
GeneNDUFB5	AuthorityHGNC:7700	Mapping file id4711 NCBI file	EvidenceTAS
GeneNDUFB6	AuthorityHGNC:7701	Mapping file id4712 NCBI file	EvidenceTAS
GeneNDUFB7	AuthorityHGNC:7702	Mapping file id4713 NCBI file	EvidenceTAS
GeneNDUFB8	AuthorityHGNC:7703	Mapping file id4714 NCBI file	EvidenceTAS
GeneNDUFB9	AuthorityHGNC:7704	Mapping file id4715 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Aerobic respiration and respiratory electron transportR-HSA-1428517261 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.