Evidence map›Paper›PMID 40873007›Full record

ArticleAutophagy2026

PPA2 activates MTFP1-DNM1L fission signaling to govern mitochondrial proliferation and mitophagy.

Soumya Ranjan Mishra, Priyadarshini Mishra, Kewal Kumar Mahapatra, Bishnu Prasad Behera, Gajanan Kendre, Moureq Rashed Alotaibi, Vijay Pandey, Birija Sankar Patro, Daniel J Klionsky, Sujit Kumar Bhutia

Abstract read
In one paragraph

Article in Autophagy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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.

Soumya Ranjan MishraCancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.
Priyadarshini MishraCancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.
Kewal Kumar MahapatraCancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.
Bishnu Prasad BeheraCancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.
Gajanan KendrePrecision Medicine and Oncology Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.
Moureq Rashed AlotaibiDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Vijay PandeyInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, P. R. China.
Birija Sankar PatroChemical Biology Section, Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, India.
Daniel J KlionskyLife Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-7828-8118
Sujit Kumar BhutiaCancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, India.ORCID 0000-0003-0962-3354

Funding

The mechanism and regulation of autophagyR35GM131919 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DANIEL J. KLIONSKY · 2019 to 2026
$6.4M
NIGMS NIH HHS R35 GM131919
6 · The paper itself

Abstract

The inorganic pyrophosphatase PPA2, a matrix-localized protein, maintains mitochondrial function. Here, we identified the role of PPA2 in activating mitochondrial fission signaling. We found that PPA2 overexpression promotes mitochondrial fission by upregulating the mitochondrial translocation of phosphorylated DNM1L S616. Moreover, PPA2 interacts with MTFP1, a mitochondrial inner membrane protein, to induce fission signaling; cells knocked down for MTFP1 and overexpressing PPA2 failed to induce DNM1L activation and subsequent mitochondrial fission. Furthermore, in physiological conditions, PPA2 directed mitochondrial fission at the midzone through MFF-DNM1L, leading to mitochondrial proliferation. Interestingly, during mitochondrial stress following CCCP treatment, PPA2 triggers peripheral fission through FIS1 and DNM1L to segregate parts of damaged mitochondria, which is essential for mitophagy. In addition, PPA2 utilized the C-terminal LC3-interacting region (LIR) of MTFP1 for mitophagy-mediated clearance of damaged mitochondria. In conclusion, PPA2 activates mitochondrial fission signaling through MTFP1-DNM1L and is essential in defining the site of mitochondrial fission, leading to mitochondrial proliferation or mitophagy for maintaining mitochondrial homeostasis.

Indexed as

DynaminsGTP PhosphohydrolasesMembrane ProteinsMitochondriaMitochondrial DynamicsMitochondrial ProteinsMitophagySignal TransductionCarbonyl Cyanide m-Chlorophenyl HydrazoneCell ProliferationHeLa CellsHumansMicrotubule-Associated ProteinsCarbonyl Cyanide m-Chlorophenyl HydrazoneDNM1L protein, humanDynaminsGTP PhosphohydrolasesMembrane ProteinsMicrotubule-Associated ProteinsMitochondrial ProteinsMitochondriamitochondrial fissionmitophagyMTFP1PPA2

Identifiers

PMID40873007
PMCPMC12758248

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.