PXD033430-3

PXD033430 is an original dataset announced via ProteomeXchange.

Title	Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction by inhibiting sirtuin mediated deacetylation
Description	Perturbed metabolism of ammonia, an endogenous cytotoxic molecule, causes mitochondrial dysfunction with decreased nicotinamide adenine dinucleotide (NAD+) in skeletal muscle. Consistent with our previous report of enrichment of NAD metabolism and sirtuin pathways during hyperammonemia, NAD+-dependent Sirtuin3 (Sirt3) expression and deacetylase activity weredecreased with increased muscle protein acetylation in murine and human skeletal muscle/myotubes. Acetylomics and cell fractions showed hyperammonemia-induced hyperacetylation of critical mitochondrial and signaling molecules. Overexpression of mitochondrial targeted Lactobacillus brevis NADH oxidase (MitoLbNOX) reversed ammonia-induced oxidative dysfunction, electron transport chain (ETC) supercomplex disassembly, lower ATP content, NAD+, and redox ratio (NAD+/NADH). Protein hyperacetylation, post-mitotic senescence and lower mitochondrial sirtuin (Sirt3) expressionduring hyperammonemia were also reversed by MitoLbNOX. Sirt3 overexpression alone did not reverse ammonia-induced redox or mitochondrial dysfunction but reversed hyperacetylation and senescence. These data show that targeting redox ratio, rather than Sirt3, more consistently restores mitochondrial homeostasis and protein acetylation during hyperammonemia.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:08:39.653.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033430
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-24 12:50:39	ID requested
1	2023-10-24 11:10:31	announced
2	2023-11-14 09:07:17	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:08:41	announced	2024-10-22: Updated project metadata.

10.6019/PXD033430;

Mishra S, Welch N, Karthikeyan M, Bellar A, Musich R, Singh SS, Zhang D, Sekar J, Attaway AH, Chelluboyina AK, Lorkowski SW, Roychowdhury S, Li L, Willard B, Smith JD, Hoppel CL, Vachharajani V, Kumar A, Dasarathy S, Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation. Aging Cell, 22(7):e13852(2023) [pubmed]

10.1111/acel.13852;

submitter keyword: multiomic, mitochondria, redox ratio, hyperacetylation,Sirtuin

Srinivasan Dasarathy
contact affiliation	Department of Inflammation and Immunity, Gastroenterology and Hepatology. Cleveland Clinic, Cleveland Ohio
contact email	dasaras@ccf.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033430
     1. Label: PRIDE project
     2. Name: Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction by inhibiting sirtuin mediated deacetylation