Evidence map›Paper›PMID 29489384›Full record

ArticleAmerican journal of physiology. Cell physiology2018

Mitochondrial inner membrane protein (mitofilin) knockdown induces cell death by apoptosis via an AIF-PARP-dependent mechanism and cell cycle arrest.

Ngonidzashe B Madungwe, Yansheng Feng, Mihaela Lie, Nathalie Tombo, Li Liu, Ferdinand Kaya, Jean C Bopassa

Open access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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

41 citing papers in PubMed, 58 citations in OpenAlex.

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  14. Depletion ofFrontiers in molecular biosciences · 2022
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  17. Towards Understanding the Involvement of HMolecules (Basel, Switzerland) · 2021
    Article
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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

7 authors at 3 institutions in 2 countries.

Ngonidzashe B MadungweDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Yansheng FengDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Mihaela LieDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Nathalie TomboDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Li LiuDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Ferdinand KayaDepartment of Ophthalmology, University of California , Davis, California.
Jean C BopassaDepartment of Cellular and Integrative Physiology, School of Medicine, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
The University of Texas Health Science Center at San Antonio · USThe University of Texas at San Antonio · USUniversity of California, Davis · US

Funding

Degradation of Mitochondrial Inner Membrane Protein Disrupts the Structural Interaction between Mitofilin and Cyclophilin D and Determines the Extent of Ischemia/reperfusion injuryR01HL138093 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BOPASSA, JEAN CHRISOSTOME · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL138093
6 · The paper itself

Abstract

Mitofilin is an inner membrane protein that has been defined as a mitochondria-shaping protein in controlling and maintaining mitochondrial cristae structure and remodeling. We determined the role of mitofilin in cell survival by investigating the mechanism underlying mitofilin knockdown-induced cell death by apoptosis. Cultured H9c2 myoblasts and HEK 293 cells were treated with mitofilin siRNA or scrambled siRNA for 24 h. Cell death (apoptosis), caspase 3 activity and cell cycle phases were assessed by flow cytometry, while cytochrome c release and intracellular ATP production were measured by ELISA. Mitofilin, apoptosis-inducing factor (AIF) and poly(ADP-ribose) polymerase (PARP) expression were measured by Western blot analysis and calpain activity was assessed using a calpain activity kit. Mitochondrial images were taken using electron microscopy. We found that mitofilin knockdown increases apoptosis mainly via activation of the AIF-PARP pathway leading to nuclear fragmentation that is correlated with S phase arrest of the cell cycle. Knockdown of mitofilin also led to mitochondrial swelling and damage of cristae that is associated with the increase in reactive oxygen species production and mitochondrial calpain activity, as well as a marked decrease in intracellular ATP production and mitochondrial membrane potential. Together, these results indicate that mitofilin knockdown by siRNA increases calpain activity that presumably leads to mitochondrial structural degradation resulting in a critical reduction of mitochondrial function that is responsible for the increase in cell death by apoptosis via an AIF-PARP mechanism and associated with nuclear fragmentation, and S phase arrest of the cell cycle.

Indexed as

AnimalsApoptosisApoptosis Inducing FactorCell Cycle CheckpointsCell DeathCell LineCytochromes cHEK293 CellsHumansMembrane ProteinsMitochondriaMitochondrial MembranesMitochondrial ProteinsMuscle ProteinsMyoblastsPoly(ADP-ribose) PolymerasesAIFM1 protein, humanApoptosis Inducing FactorCytochromes cIMMT protein, humanMembrane ProteinsMitochondrial ProteinsMuscle ProteinsPoly(ADP-ribose) PolymerasesReactive Oxygen SpeciesRNA, Small InterferingAIF-PARP-pathwayapoptosiscell cycle arrestcell deathH9c2 cardiomyoblastHEK 293 cell linemitochondria cristae morphology and functionmitochondrial inner membrane protein (mitofilin)

Identifiers

PMID29489384
PMCPMC6087732
OpenAlexW2788072287

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.