Journal article
Mitochondria-Lysosome Related Organelles Mediate Mitochondrial Clearance During Cellular Dedifferentiation
Cell reports (Cambridge), Vol.42(10), 113291
10/01/2023
DOI: 10.1016/j.celrep.2023.113291
PMCID: PMC10842364
PMID: 37862166
Abstract
Dysfunctional mitochondria are removed via multiple pathways such as mitophagy, a selective autophagy process. Here, we identify an intracellular hybrid mitochondria-lysosome organelle (termed the mitochondria-lysosome related organelle, MLRO) which regulates mitochondrial homeostasis independent of canonical mitophagy during hepatocyte dedifferentiation. MLRO is an electron dense organelle that has either a single or double membrane with both mitochondria and lysosome markers. Mechanistically, MLRO is likely formed from the fusion of mitochondria derived vesicles (MDVs) with lysosomes through a PARKIN, ATG5, and DRP1-independent process, which is negatively regulated by transcription factor EB (TFEB) and associated with mitochondrial protein degradation and hepatocyte dedifferentiation. MLRO, which is galectin 3 positive, is reminiscent of damaged lysosome and could be cleared by overexpression of TFEB resulting in attenuation of hepatocyte dedifferentiation. Together, results from this study suggest that MLRO may act as an alternative mechanism for mitochondrial quality control independent of canonical autophagy/mitophagy involved in cell dedifferentiation.
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•Dedifferentiated hepatocyte induces mitochondria-lysosome related organelle (MLRO).•MLRO is a hybrid organelle formed by lysosomes fuse with mitochondria derived vesicles.•MLRO is independent of autophagy/mitophagy machinery and negatively regulated by TFEB.
Hepatocyte dedifferentiation is a common feature for chronic liver diseases such as alcohol-associate hepatitis and metabolic dysfunction-associated steatohepatitis. Ma et al reported that hepatocyte dedifferentiation is associated with MLRO induction that can be reversed by TFEB-mediated removal of leaky lysosomes.
Details
- Title: Subtitle
- Mitochondria-Lysosome Related Organelles Mediate Mitochondrial Clearance During Cellular Dedifferentiation
- Creators
- Xiaowen Ma - University of Kansas Medical CenterSharon Manley - University of Kansas Medical CenterHui Qian - University of Kansas Medical CenterYuan Li - University of Kansas Medical CenterChen Zhang - University of Kansas Medical CenterKevin Li - University of Kansas Medical CenterBenjamin Ding - University of Kansas Medical CenterFengli GuoAllen Chen - University of Kansas Medical CenterXing Zhang - Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USAMeilian Liu - Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USAMeihua Hao - Department of Anatomy and Cell Biology, Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USABenjamin Kugler - University of Kansas Medical CenterE Matthew Morris - University of Kansas Medical CenterJohn Thyfault - University of Kansas Medical CenterLing Yang - University of IowaHiromi Sesaki - Johns Hopkins University School of MedicineHong-Min Ni - University of Kansas Medical CenterHeidi McBride - McGill UniversityWen-Xing Ding - University of Kansas Medical Center
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.42(10), 113291
- DOI
- 10.1016/j.celrep.2023.113291
- PMID
- 37862166
- PMCID
- PMC10842364
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/01/2023
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984489660202771
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