Evidence map›Paper›PMID 40685746›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Mortalin and PINK1/Parkin-Mediated Mitophagy Represent Ovarian Cancer-Selective Targets for Drug Development.

Vishal Chandra, Justin Garland, Rajani Rai, Donghua Zhao, Charuksha Walgama, Sadagopan Krishnan, Andrew T Long, Tongzu Liu, Laura Adhikari, Doris M Benbrook

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
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  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Vishal ChandraGynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.ORCID https://orcid.org/0000-0003-3765-377X
Justin GarlandPathology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.ORCID https://orcid.org/0009-0002-3771-5248
Rajani RaiGynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.ORCID https://orcid.org/0000-0003-3503-5265
Donghua ZhaoDepartment of Physics, Oklahoma State University, Stillwater, OK, 74078, USA.ORCID https://orcid.org/0000-0002-6638-4014
Charuksha WalgamaDepartment of Chemistry, Oklahoma State University, Stillwater, OK, 74078, USA.
Sadagopan KrishnanDepartment of Chemistry, Oklahoma State University, Stillwater, OK, 74078, USA.ORCID https://orcid.org/0000-0002-9968-2712
Andrew T LongBiochemistry Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Tongzu LiuGynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Laura AdhikariPathology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Doris M BenbrookGynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.ORCID https://orcid.org/0000-0001-7606-8245

Funding

Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ROBERT S. MANNEL · 2018 to 2026
$27.1M
Ovarian Cancer ChemopreventionR01CA196200 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BENBROOK, DORIS MANGIARACINA · 2015 to 2019
$2.5M
Mechanism of SHeA2 Action in Ovarian CancerR01CA106713 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BENBROOK, DORIS MANGIARACINA · 2005 to 2009
$1.3M
NCI NIH HHS HHSN261201500038CNCI NIH HHS P30 CA225520NCI NIH HHS P30CA225520NCI NIH HHS R01 CA106713NCI NIH HHS R01CA106713NCI NIH HHS R01 CA196200NCI NIH HHS R01CA196200
6 · The paper itself

Abstract

Mortalin is an essential chaperone for the import of nuclear-encoded proteins into mitochondria and is elevated in ovarian cancer in association with poor patient prognosis. The investigational new drug, SHetA2, interacts with mortalin releasing its client proteins. In this study, interactions of SHetA2 moieties and mortalin substrate binding domain (SBD) amino acids are demonstrated by surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) to occur at low micromolar SHetA2 concentrations that selectively kill cancer cells over noncancerous cells. In both ovarian cancer and noncancerous cells SHetA2 reduces: mitochondria import of mortalin, degradation of mortalin's mitochondrial localization sequence (MLS), mortalin/inositol 1,4,5-trisphosphate receptors complexes and oxidative phosphorylation. In cancer cells only, SHetA2 reduces calcium levels, mitochondrial length and fusion proteins, while inducing autophagy and PTEN-induced kinase 1 (PINK1)/PARKIN-mediated mitophagy. Noncancerous cells exhibit increased mitochondrial branch length in response to SHetA2 and a low level of inducible autophagy that is resistant to SHetA2. Inhibition of autophagosome-lysosome fusion reduces, or increases, SHetA2 cytotoxicity in ovarian cancer or noncancerous cells, respectively. SHetA2 inhibits mortalin and growth, and induces mitophagy in ovarian cancer xenografts and increases survival post-surgical tumor removal. In conclusion, SHetA2 binds directly to mortalin's SBD and causes distinct responses in ovarian cancer and noncancerous cells.

Indexed as

MitophagyOvarian NeoplasmsProtein KinasesUbiquitin-Protein LigasesAnimalsCell Line, TumorDrug DevelopmentFemaleHSP70 Heat-Shock ProteinsHumansMiceMitochondriaPTEN-Induced Putative KinaseHSP70 Heat-Shock Proteinsmortalinparkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein Ligasesautophagymitochondrial networkingmitophagyPINK1SHetA2

Identifiers

PMID40685746
PMCPMC12499392

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.