PXD014252

PXD014252 is an original dataset announced via ProteomeXchange.

Title	Identification of ALDH6A1 as a Potential Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome
Description	Various liver diseases, including hepatocellular carcinoma (HCC), have been linked to mitochondrial dysfunction, a condition characterized by abnormal levels of nitric oxide (NO) and reactive oxygen species (ROS). In this study, we subjected the human liver mitochondrial proteome to an extensive quantitative proteomic profiling analysis and molecular characterization to identify potential signatures indicative of cancer cell growth and progression. A sequential proteomic analysis identified 2452 mitochondrial proteins, of which 1464 and 2010 were classified as normal and HCC mitochondrial proteins, respectively, with 1022 overlaps. Further metabolic mapping of the HCC mitochondrial proteins narrowed our biological characterization to four proteins, namely ALDH4A1, LRPPRC, ATP5C1 and ALDH6A1. The latter protein, a mitochondrial methylmalonate semialdehyde dehydrogenase (ALDH6A1), was most strongly suppressed in HCC tumor regions (~10-fold decrease) and was predicted to present in plasma. Accordingly, we selected ALDH6A1 for a functional analysis. Interestingly, much lower NO levels were detected in both HCC tumor regions and an ALDH6A1-overexpression (O/E) cell line than in control (Hep3B) cells and could be restored by treatment with S-nitroso-N-acetyl-penicillamine. In contrast, ALDH6A1-O/E cells exhibited an approximately 50% increase in ROS levels and decreased lactate levels relative to control cells. Propidium iodine staining suggested that the abnormal decrease in NO and increase in ROS could be caused by depolarization of the mitochondrial membrane potential (ΔΨ). We propose that an attenuated ALDH6A1 level may subsequently promote uncontrolled cell growth and proliferation, act as a signature for assessing HCC progression and treatment responses.
HostingRepository	PRIDE
AnnounceDate	2020-01-29
AnnouncementXML	Submission_2020-01-29_05:46:34.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD014252
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Heon Shin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-arginine residue; L-cysteine residue; residues isobaric at 113.084064 Da; L-histidine residue; Phospho; residues isobaric at 128.058578 Da; L-lysine residue; Oxidation; L-tyrosine residue; L-proline residue; Carbamidomethyl; residues isobaric at 71.037114 Da
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-13 06:07:56	ID requested
⏵ 1	2020-01-29 05:46:36	announced

Shin H, Cha HJ, Lee MJ, Na K, Park D, Kim CY, Han DH, Kim H, Paik YK, Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome. J Proteome Res, 19(4):1684-1695(2020) [pubmed]

submitter keyword: ALDH6A1, hepatocellular carcinoma, mitochondria, nitric oxide, reactive oxygen species

Young-Ki Paik
contact affiliation	Yonsei Proteome Research Center
contact email	paikyk@gmail.com
lab head
Heon Shin
contact affiliation	Yonsei University
contact email	shinh@proteomix.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014252
     1. Label: PRIDE project
     2. Name: Identification of ALDH6A1 as a Potential Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome