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Mitochondria

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Mitochondria

This topic page reorganises the 19 source notes filed under mitochondria into reading-order axes. It does not replace the by-photo Markdown; every claim links back to a source note or the canonical transcription. Where a source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Overview

The corpus treats mitochondria as seven overlapping problems. (1) Foundational biology — cellular respiration, mitochondrial structure, ETC complexes I-V, Complex I subunit table and rotenone-binding site mapping (20240722_183439, 20240722_183442, 20240722_183446, 20240722_183449). (2) Mitochondrial DNA — copy number, structure, the 37-gene Cambridge Reference Sequence, methylation, turnover, transcription/biogenesis, dynamics, and mitochondrial regulators (TRAP1, HTRA2/PARK13) (20240722_183452). (3) The Assessment of mitochondria summary matrix that crosses biogenesis (pS65-Ub, Parkin, TOM40/20, mtDNA copy number), somatic damage, cardinal/function items (ATP, MMP, MC1 activity, OCR, NFP, methylated mtDNA) with feasibility/ variability/evidence columns (20240722_183455, 20240722_183458, 20240722_183501, 20240722_183505). (4) 31P MRS imaging as a candidate in-vivo bioenergetics readout (20240722_183505, 20240722_183508, 20240722_183511). (5) MC1 PET with the [18F]BCPP-EF / [3H]BCPP-EF tracer family — mechanism, MIND-MAPS human studies, MPTP-monkey work, and the Preclinical-support live-cell vs homogenate radioligand-binding assay log (20240722_183524, 20240722_183528, 20240722_184135). (6) Mitophagy biology and in-vivo measurement candidates (PINK1-Parkin pathway, mt-Keima / TOLLES / mt-SRAI probes, Padmanabhan 2019 MJFF biomarker pipeline) (20240722_184146, 20240722_184149). (7) TRAP1 as a mitochondrial regulator and the Amathus PAM program (20240722_184535). The MEG / Maiko Tanaka / Metabolomics / MIBG strand (20240722_183426, 20240722_183432) sits at the edge of this section as adjacent rather than core mitochondrial-mechanism evidence. The mitophagy / pS65-Ub / PINK1-Parkin biology and the Parkin-PD fibroblast lines that anchor the [3H]BCPP-EF assay work are covered as separate topics; see parkin for that material rather than re-quoting it here.

Source Coverage

19 source notes are assigned to the mitochondria section. They sit across 16 first-level nav_path clusters; the topic axes below collapse those clusters as follows:

nav root (first nav_path entry)sourcescovered axis
Structure of mitochondria2Mitochondrial structure / ETC / Complex I subunits / MAM / σ1R imaging
Mitochondrial Regulators2Assessment matrix continuation / circulating cell-free mitochondria / mtDNA
Summary2Assessment of mitochondria summary matrix / 31P MRS imaging block
Function1Cellular respiration steps
Mitochondrial DNA home…1Mitochondrial Respiratory Complexes (I-V) reference / rotenone-binding sites
Mitochondrial DNA1mtDNA copy/structure, 37-gene Cambridge Reference Sequence, methylation, turnover, biogenesis, dynamics, regulators
Assessment of mitochond...1mtDNA damage / methylation / cytokines / metabolomics / FDG-PET / phosphatidylethanolamine / NFP / 31P MRS principle table
Studies of 31P MRS1ATP supply/consumption diagram / 7T 3D 31P MRS-MT / metabolite peaks / REPAIR-PD reference
Genes Mitochondria1MitoCarta3.0 / Billingsley 2019 PRS / MC1 PET tracer mechanism / MIND-MAPS / MPTP-monkey
PRS Mitochondria1Preclinical-support [3H]BCPP-EF assay log / saturation analysis planning / fibroblast cohort
USA's group1Radioligand binding study theory (Tsukada 2014 / Kazami 2019; saturation / competition / kinetic assay primer)
MOA of Mitophagy1PINK1-Parkin mitophagy MOA / mt-Keima / MC1 PET in FA / microdialysis
mitophagy in vivo…1mitophagy probe comparison (EGFP-mCherry / TOLLES / mt-SRAI) / Padmanabhan biomarker pipeline / BMx Milestones / MRI Classification
Magnetoencephalography (MEG)1MEG principle / Network-Rodriguez 2023 PPMI metabolomics / MSA aSyn PFF
Maiko Tanaka1Takeda playbook PE / CS / NS DDU 6/21 stage requirements
TRAP11TRAP1 protein / MOA / Amathus PAM in vitro pharmacology log

For exact nav_path strings and headings see mitochondria and the matching by-nav indexes listed in related_topics_by_nav.

Across the 19 sources, the source-note frontmatter records 85 uncertain_span_count entries and 0 body-embedded figure assets. The zero-figure-embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md): the mitochondria pages embed published Western blot panels, dataset plots, ATP supply/consumption schematics, MR spectroscopy spectra, saturation- and competition-binding curves, and 96-well plate maps inside crops that also carry table or label text, so they are kept as evidence rather than embedded. The 85 uncertain spans are retained as review targets and not resolved here.

Foundational Biology: Respiration, Structure, Complex I, MAM

20240722_183439 is the Function > Steps of cellular respiration page. It carries the four-step glycolysis → pyruvate oxidation → citric acid cycle → oxidative phosphorylation summary, the Keeney 2006 Figure 2 Complex I subunit Western blot table (CTL vs PD at 39/30/20/15/8 kDa subunits, with the 20 kDa and 8 kDa columns marked significant), the Pyle 2016 #946 mtDNA- copy-number panels (PBC / SNpc / FC), and a multi-tissue mitochondrial- activity literature table covering fibroblast / skeletal muscle / platelets / lymphocytes / PBMC / monocyte / leukocyte / spermatozoa / serum. Specific cell values are image- or table-primary on the source page; 5 Uncertain Spans are recorded there.

20240722_183442 is the Structure of mitochondria page (location, size, ETC-complex header strip, structural table from outer membrane through cristae and the mitochondrial network, oxidoreductase / electron-flow nomenclature block, and the start of the MITOCHONDRIAL RESPIRATORY CHAIN: COMPOSITION reference table). 6 Uncertain Spans covering small ETC diagram labels, the MITOCHONDRIA-STRUCTURE caption, mitochondrial- network adjacency-matrix readings, TOM5/6/7 line ends, a truncated molecular-mass URL, and inner-membrane right-most column placement.

20240722_183446 (Mitochondrial DNA home… > … > Structure of mitochondria > Rotenone) is the rotenone-binding-site reference page: the wide Lawson/Wirth- 2016 Mitochondrial Respiratory Complexes (I-V) table (per-complex inhibitors, nuclear DNA / mtDNA subunit counts, and disorder lists), the Bos-taurus-to-human-gene mapping for the Rotenone-binding / Common-MC1-inhibitor / Catalytic-core sites (PSST / 49 kDa / TYKY / ND subunits / 30, 75, 51, 24 kDa entries), and the rotenone-binding / ubiquinone-reduction-site paragraphs (with Degli Esposti 1998 #1163 type-A/B/C inhibitor classification). The source flags 4 Uncertain Spans, including the inline Korean note that human PSST is absent so the human rotenone-binding site is not unambiguously assigned in the 2016 Wirth reading — that uncertainty stays on the source page rather than being resolved here.

20240722_183449 is the detailed Subunits of complex I Wirth-2016 table (~45 NDUFS / NDUFV / NDUFA / NDUFB / NDUFC entries cross-mapped to Bos taurus / Yarrowia lipolytica / Pichia thermophila / Paracoccus denitrificans / Escherichia coli, with five highlighted human entries) plus the MAM (Mitochondria-associated membranes) Veeresh 2019 #1298 reference figure and the start of the Imaging of MAM table — the σ1R tracer [¹¹C]SA-4503 sits alongside ¹⁸F-BCPP-EF and ¹¹C-UCB-J in the same MIND-MAPS-style imaging block, but the MC-I content is anchored under the MC1 PET axis below. 4 Uncertain Spans (species-name reading, NDUFA9 row mapping, right-cropped tracer column, yeast Mdm10/12/34/ Mmm1 labels).

Mitochondrial DNA, Genes, Methylation, Turnover, Dynamics, Regulators

20240722_183452 is the single dense Mitochondrial DNA page that walks across copy number, structure, the 37-gene Cambridge Reference Sequence (13 protein-coding subunits, 22 tRNAs, 2 rRNAs), methylation, turnover, transcription / biogenesis (TFAM, MitoPark mouse), dynamics (OPA1 / MFN1 / MFN2 / Drp1), the regulators table (TRAP1 and HTRA2 / PARK13, with Fitzgerald 2017 #1289 naming TRAP1 as an HTRA2 interactor), and circulating cell-free mitochondria (Al Amir Dache 2020) — all in one nav_path string. Specific cell values, gene-list strands, and citation digits are table-primary on the source page; 4 Uncertain Spans (top genome-figure labels, MT-RNR2 Humanin row, methylation- bullet typography, citation key clip) are flagged there.

Assessment Of Mitochondria Summary Matrix

The four-page summary block builds a single decision matrix for candidate mitochondrial biomarkers across feasibility, variability, and evidence-in-PD columns. None of the cell values below are re-quoted here; the source pages should be opened directly.

  • 20240722_183455 is the matrix page itself (rows: pS65-Ub, Parkin, TOM40/20, mtDNA copy number, Mt DNA damage, ATP production / ATP basal, MMP, MC1 activity, OCR, Phosphatidylethanolamine, NFP, Methylated mtDNA; feasibility / variability / evidence-in-PD columns), the good / Not good criterion table, the rationale block, and the Δψm reference block (JC-1 / TMRM / MitoTracker biology; Chou 2017 #1048; Cleeter / CCCP / FCCP literature). 6 Uncertain Spans.
  • 20240722_183458 is the assay-literature panel for MMP, circulating cell-free mitochondria, mitochondrial mass, MC1 / MC2 / MC4 activity (rotenone-sensitive vs -insensitive assays; van der Merwe 2014 #722 NADH ferricyanide reductase), Mito membrane proteins (TOM40 / 20 / ANT1 / VDAC / PHB2 / CD171), Mito O2 consumption, Cutaneous respirometry, Seahorse flux analysis, and oxygen extraction fraction. 3 Uncertain Spans.
  • 20240722_183501 continues the matrix into ATP synthesis (per-complex ADP phosphorylation; Mortiboys digitonin-treated fibroblast protocol), ATP basal (MPP+ literature; ATPlite kit), the MC I subunit list (Grünewald 2016 #1071 antibody panel; the Keeney 2006 Fig. 2 CTL/PD subunit table is reproduced on this page too), per-subunit reference notes, biogenesis transcription factors, mitophagy readouts, and the mtDNA copy number / damage block (Grünewald 2016 #935 triplex real-time PCR for ND1/ND4/D-loop; Sanders 2014 #1411 ARP staining for abasic sites). 5 Uncertain Spans.
  • 20240722_183505 closes the matrix with mtDNA damage (ARP / qPCR / Andolina patent / Dölle 2016 #1416 / Detroit R&D commercial kit / Qi 2023 #2429), Methyl mtDNA (Blanch 2016 #1355), cytokines (FGF-21, GDF-15; Davis 2020 PMID 32190419 box plots; Miyaue 2020 #1339), serum lactate / Metab imaging / DNP ¹³C-MRS, FDG PET, Phosphatidyl- ethanolamine, N-formyl peptides (NFP), and the start of the 31P MRS Imaging principle block. 4 Uncertain Spans.

Specific matrix cells, citation digits, and decision thresholds are image- or table-primary on the source pages; reading order should be the source pages themselves rather than this synthesis.

31P MRS Imaging

20240722_183505 opens the 31P MRS Imaging > Principle block at the bottom of the Assessment-matrix page (Magnetization transfer definition, PCr-energy- buffer biology, ATP generation / consumption / CK reaction / ATP resynthesis four-column table).

20240722_183508 is the Studies of 31P MRS page proper. It anchors on the Schlattner 2016 #1589 ATP supply / consumption schematic, the rate-of-PCr-recovery as indicator of mitochondrial oxidative capacity, the indirect [ADP] calculation (Hattingen 2009 #1569 formula and Iotti 2005 constants preserved verbatim on the source page), the Zhu 2018 #1119 finding that brain ATP concentration remains constant across anesthesia despite ~50% CMR_ATP changes, the 7T 3D 31P MRS-MT imaging method (grey- vs white-matter CMR_ATP / CMR_CK comparison), the phosphorus- containing-metabolites list, and the Cellular Respiration / three- spin-exchange schematic. 6 Uncertain Spans (small abbreviation labels in the supply / consumption diagram, CMR-subscript spelling, formula exponents, principle spectrum panel labels, ©Springer credit, Long acquisition tie/time clip).

20240722_183511 carries the Summary > 31P MRS imaging > Principle > Studies of 31P MRS human-cohort comparison table and the Christen Klein clinical-trial block. The Prasuhn 2019 #1475 / 2020 #1476 method block records the double-tuned P-headcoil sequence parameters and AMARES peak-fitting; the clinical-trial sub-table records P1 University of Minnesota UDCA NCT02967250, P2 University of Sheffield UDCA The "UP" Study NCT03840005 (PI Oliver Bandmann), and a third Sheffield single-arm 6-week UDCA dose-escalation study with three subjects’ pre/post-UDCA ATP concentrations preserved verbatim. Animal references include Naritomi 1988 #1317 / Crockard 1987 #1316 (gerbil), Bainbridge 2014 #1118 (piglet), Obrenovitch 1988 #1202 (baboon, tissue extract), Oláh 2008 #1594 (HD TG mice, biochemical). The Studies of 31P MRS — comparison table lists Eleff 1990 #1582 / Montagna 1992 #1583 / Barbiroli 1993 #1588 / Hu 2000 #1584 / Hattingen 2009 #1585 (twice, in different regions and field strengths) / Montagna 1993 / Barbiroli 1999 #1586 / Rango 2006 #1587, with per-row %-changes preserved verbatim on the source page (and the inline Korean caveat 못 믿음 (ATP 를 Assume) flagging the Hu 2000 row that assumed ATP = 3 mM). The Bandmann questions block (Fibroblast / Any Parkin-PD patients? / P trial) closes the page. 4 Uncertain Spans.

MC1 PET / Radioligand Binding (BCPP-EF Family)

20240722_183524 is the Genes Mitochondria > PRS Mitochondria > MC1 PET > MC1 PET studies hub. The genes / PRS block covers MitoCarta3.0 and the Billingsley 2019 #1190 sPD primary / secondary mito-gene PRS work (Mendelian randomisation via eQTL; MRPS34 / MRPL43 alterations in sPD blood). The MC1 PET block introduces the [18F]BCPP-EF tracer mechanism per Kazami 2019 #874 (BCPP compounds binding MC-I at the rotenone site; PET imaging doses far below the IC50 so the tracer is physiologically inactive and does not inhibit MC1) and McCluskey 2020 #485 (only [18F]BCPP-EF for brain MC1 imaging). The MC1 PET studies table records Wilson 2020 #902 / MIND-MAPS, Mansur 2018 #876 and Mansur 2021 #2013, and Tsukada 2016 #734 (MPTP monkey, MC-I vs DAT-PET correlation); the per-cohort numbers are table-primary on the source page. 4 Uncertain Spans.

20240722_183528 is the USA's group continuation page that pairs (a) the Tsukada 2014 #883 / #884 and Kazami 2019 #1082 SMP-binding study summaries (with IC50 values and BCPP-EF lipophilicity preserved on the source page) with (b) a Radioligand binding study primer (specific vs non-specific binding; self vs heterologous blocking; saturation / competition / kinetic assay matrix; Table 7.5.2 Evaluating-the-Assumptions opening rows). 4 Uncertain Spans. The page is methodological background rather than a study readout, so it is anchored here without being re-quoted.

20240722_184135 is the Preclinical support deep-dive on the [3H]BCPP-EF assay-development log: a multi-iteration date-stamped table (Updates 20211210, 20220108, 20220215, 20220518) covering homogenate vs living-cell formats, wash protocols, and saturation analysis planning, plus a fibroblast cohort with HC (GM01650, 106-05n, CC-2511), PKRN-PD (ND31618, ND30171, ND40078) and sPD (ND37132, ND30159) tissue masses. Iteration values (CPM percentages, plate maps, mg amounts) are table-primary on the source page. 5 Uncertain Spans. The same Parkin-PD fibroblast set is discussed under parkin; that material is not re-stated here.

Mitophagy Biology And In-Vivo Measurement

20240722_184146 is the MOA of Mitophagy page. It opens with an MJFF RFP timeline and a proposed MC1 PET [18F]BCPP-EF imaging in Parkin-PD patients study design (Mortiboys 2008 / Bogetofte 2019 rationale, Invicro London cross-sectional design, ~18% between-participant variability allowing detection at 80% power, ~12-month timeline; specific budget and power figures stay on the source page). The page also carries the MC1 PET in FA Rabiner protocol, a Microdialysis sub-section, the detailed PINK1-Parkin MOA grid (PINK1 cleavage cycle by TIM/PARL; ubiquitin Ser65 phosphorylation; Parkin recruitment, dimerisation, full activation; ubiquitylation of MOM substrates; receptor recruitment to ubiquitin chain; LC3-mediated autophagosome wrapping), the CCCP uncoupling definition, and the start of the Mitophagy Probes table. 5 Uncertain Spans.

20240722_184149 is the mitophagy in vivo… > Monthly update > MRI > Classification page. It extends the mitophagy-probe table (EGFP-mCherry, TOLLES per Katayama 2020 #769, YPet, mt-SRAI), lists candidate in-vivo readouts with the Takeshi vs Misa argument-and-counterargument framing, and preserves the MJFF / Padmanabhan 2019 #820 biomarker-pipeline figure (Parkin ligase activity ELISA / pS65Ub MSD / Miro ELISA / mtDNA copy-number Real-time PCR / MMP / Cori flux / Mfn1/2 Immunoblotting). The Monthly-update GBA-PD GT block and the BMx Milestones FY2020- FY2023 Gantt timeline (PE Parkin PET / pS65-Ub / MC1 Imaging / DaTSCan readouts) are operations-side material; the MRI Classification section at the bottom is a Wikipedia-style sequence taxonomy adjacent to the mitochondria scope through the in-vivo nav root rather than the mechanism. 4 Uncertain Spans.

The PINK1-Parkin upstream biology, pS65-Ub as biomarker, NBB sample values, and the Hou 2018 #819 progression figure live on parkin; this topic page does not re-state it.

TRAP1

20240722_184535 is the single TRAP1 > MOA page. It carries the tail of a bulk- and single- cell transcriptomics plan, a Midbrain DA neurons mini-table, and the TRAP1 gene / protein / function block (HSP75 / mitochondrial Hsp90 family; PINK1 substrate; N-terminal ATPase / middle / C-terminal dimerisation domain) with the function-column literature (downstream of PINK1 and MC-I; modulates spare respiratory capacity; inhibits SDHA / cytochrome c oxidase; hypoxia induction; rescues HTRA2 / PINK1 mitochondrial dysfunction; Gaare 2018 #1288 No evidence for rare TRAP1 mutations influencing the risk of idiopathic PD). The Pipeline column names Amathus: TRAP1 positive allosteric modulator (PAM) and points to a Box ShareFolder URL. The wide MOA grid (normal / PINK1-phosphorylates-TRAP1 / ↑TRAP1-phosphorylation / Client- proteins states), the Tx Hypothesis row, and the in vitro pharmacology progress log (date-stamped 20230914 / 20231005 / 20231018 / 20231130 entries with Amathus PAM ADP-Glo / client-protein / ROS assay readouts) are table-primary on the source page; right- edge progress columns continue into 20240722_184539 (which sits outside the mitochondria section). 4 Uncertain Spans. TRAP1 is treated here as an axis within the Mitochondria topic and not as a separate entity page; the Amathus PAM program description is preserved on the source page rather than re-stated here.

MEG / Maiko Tanaka / Metabolomics / MIBG (Adjacent Strand)

20240722_183426 is the Magnetoencephalography (MEG) > Maiko Tanaka > Metabolomics > MIBG page: Denali PTV.IDS / PTV:PGRN BMP datasets, BMP / LAMP-1 / PGRN responsibility planning, a Comp Bio Lysosomal-Targets scoring suggestion, Wang 1974 turnover, a Random Forest / ensemble note, the MEG axis itself (Singh 2014 #2464; Boon 2019 #2466), the Maiko Tanaka MSA strand, the Network-Rodriguez 2023 #2347 PPMI plasma LC-MS metabolomics row, and the start of the Milestones (process) table. 5 Uncertain Spans. 20240722_183432 is the continuation page that preserves the Takeda-internal Portfolio Entry / Candidate Selection / NS DDU 6/21 / Pre-Clinical Stages playbook slides. 3 Uncertain Spans. Both pages are filed in this section because their first nav roots sit inside the Maiko Tanaka MEG / Metabolomics / MIBG / Milestones cluster; the playbook content is operations rather than mitochondrial mechanism, so it is anchored here without re-quotation.

Source Table

All 19 sources, in capture-time order, with the per-page uncertain-span and embedded-image counts copied from front matter. nav path is the full nav_path recorded in the source note.

stemnav path / headingsource notecanonicaluncertain spansembedded images
20240722_183426Magnetoencephalography (MEG) > Maiko Tanaka > Metabolomics > MIBGnotemd50
20240722_183432Maiko Tanaka > Metabolomics > MIBG > Milestones (process)notemd30
20240722_183439Function > Steps of cellular respirationnotemd50
20240722_183442Structure of mitochondrianotemd60
20240722_183446Mitochondrial DNA home… > Location of mitochondria > Structure of mitochondria > Rotenonenotemd40
20240722_183449Structure of mitochondria > Mitochondrial respiratory chain complexes > Subunits of complex I > MAM (Mitochondria-associated membranes) > Imaging of MAMnotemd40
20240722_183452Mitochondrial DNA > Mitochondrial genes > Methylation of mt DNA > Mitochondrial turnover > Mitochondrial transcription (biogenesis) > Mitochondrial DYNAMICS (fusion/fission and transportation) > Mitochondrial Regulators > Circulating cell-free mitochondria in bloodnotemd40
20240722_183455Summarynotemd60
20240722_183458Mitochondrial Regulators > Circulating cell-free mitoch… > Assessment of mitochond… > Summarynotemd30
20240722_183501Mitochondrial Regulators > Circulating cell-free mitochondrial DNA > Assessment of mitochondrial function > Summarynotemd50
20240722_183505Assessment of mitochond… > Summary > 31P MRS imaging > Principlenotemd40
20240722_183508Studies of 31P MRSnotemd60
20240722_183511Summary > 31P MRS imaging > Principle > Studies of 31P MRSnotemd40
20240722_183524Genes Mitochondria > PRS Mitochondria > MC1 PET > MC1 PET studiesnotemd40
20240722_183528USA’s groupnotemd40
20240722_184135PRS Mitochondria > MC1 PET > MC1 PET studies > Preclinical supportnotemd50
20240722_184146MOA of Mitophagynotemd50
20240722_184149mitophagy in vivo… > Monthly update > MRI > Classificationnotemd40
20240722_184535TRAP1 > MOAnotemd40

Totals across the 19 sources: uncertain_span_count = 85, embedded_image_count = 0. These are review surface area; the zero-figure-embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md) under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded.

Uncertainties Carried Forward

This page deliberately does not paraphrase the assessment-of- mitochondria summary-matrix cell values, the Cambridge Reference Sequence 37-gene table, the Complex I subunit table cell values, the rotenone-binding-site / catalytic-core mapping, the Schlattner ATP supply/consumption diagram inner labels, the Hattingen [ADP] formula exponents, the Studies-of-31P-MRS comparison-table %-changes, the Tsukada / Kazami / Mansur / Wilson MC1 PET tracer numbers, the Preclinical-support [3H]BCPP-EF iteration log values, the mitophagy MOA grid column boundaries, or the TRAP1 in-vitro pharmacology progress-narrative cells. Specific uncertainty hot spots worth checking before any downstream extraction:

The cross-source Assumed [ATP] = 3 mM convention recurring across Hu 2000 / Hattingen 2009 / Du 2007 / Oláh 2008 is preserved verbatim on each source page; the 못 믿음 (ATP 를 Assume) Korean-shorthand caveat on 20240722_183511 is preserved as the source’s own reservation rather than reconciled.

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