PXD068316-1

PXD068316 is an original dataset announced via ProteomeXchange.

Title	Accumulated mtDNA mutations specifically impair complex I-linked respiration
Description	Oxidative phosphorylation (OxPhos) within mitochondria relies on the coordinated synthesis of both nuclear- and mitochondrial-encoded protein subunits comprising the mitochondrial respiratory complexes (Complexes I–V). Mitochondrial DNA (mtDNA) encodes 13 proteins vital for Complex I, III, IV, and V function. Accumulated mutations in mtDNA are causally linked to aging and several age-related diseases, presumably as a consequence of impaired respiration. However, how high mtDNA mutation burden impinges on cellular bioenergetics across the major organ systems remains only partially resolved. Due to the growing links connecting mtDNA mutations to human pathophysiology, here we leveraged a comprehensive mitochondrial phenotyping platform to assess the phenotypic consequences of increased mtDNA mutation burden across tissues (brown adipose, brain, colon, heart, kidney, liver, lung, and bone marrow-derived mononuclear cells) of the mouse. Remarkably, despite widespread reductions in OxPhos protein expression, mitochondrial respiratory capacity under mixed substrate conditions was largely preserved across tissues. More detailed analysis revealed that NAD-linked respiration exhibited partial functional deficits in most tissues, consistent with functional deficiencies in complex I. In contrast, respiration routed from CII-CIII-CIV-CV remained intact. Together, these findings highlight Complex I as the primary functional consequence of mtDNA mutational load.
HostingRepository	jPOST
AnnounceDate	2026-02-19
AnnouncementXML	Submission_2026-02-19_13:43:31.153.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelsey Fisher-Wellman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-12 06:20:03	ID requested
⏵ 1	2026-02-19 13:43:31	announced

Dataset with its publication pending

submitter keyword: PolG, mitochondria, complex I

Kelsey H Fisher-Wellman
lab head
Kelsey Fisher-Wellman
contact affiliation	Wake Forest University
dataset submitter

jPOST dataset URI

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