Bacterial FtsZ induces mitochondrial fission in human cells
Posted on: 24 February 2020 , updated on: 18 June 2021
Preprint posted on 24 January 2020
Does the mitochondrial inner membrane possess a unique fission machinery? Spier et al. show that FtsZ, which is a protein responsible for bacterial division, induces mitochondrial inner-membrane fission when expressed in human mitochondria.
Selected by Leeba Ann ChackoCategories: cell biology, evolutionary biology
Background:
Mitochondria are dynamic tubular organelles that constantly undergo fission and fusion events inside the cell. These dynamics are regulated by specific proteins. For instance, fusion of the mitochondrial outer membrane (OMM) is regulated by mitofusin 1 and mitofusin 2 (MFN1 and MFN2) while fission is mediated by the dynamin-related protein 1 (DRP1). Likewise, fusion of the inner mitochondrial membrane (IMM) is brought about by the dynamin-like GTPase optic atrophy 1 (OPA1)1. Interestingly, how IMM fission occurs remains elusive. Two IMM proteins, namely, MTP18 and S-OPA1 have shown to affect mitochondrial morphology, however, the mechanism through which they induce mitochondrial fission is not well understood2. Spier et al. address this question by looking at the evolutionary past of mitochondria for clues.
Today, it is widely accepted that mitochondria do not form de novo and evolved from a proteobacterial lineage3. It has been shown that some of these proteobacteria possess inner membrane invaginations similar to what is seen in mitochondrial cristae. Several unicellular eukaryotes have a mitochondrial FtsZ4 , however, the division machinery of mitochondria in metazoan or fungal cells involving DRP1 is not like what is observed in bacteria involving the Z-ring forming protein, FtsZ5,6. This suggests that there is no evolutionary conservation of the division machinery between the bacteria and mitochondria of opisthokonts (fungi and metazoan). To test whether human mitochondria have completely lost their ancestral bacterial division machinery, Spier et al. introduced a human codon-optimized version of FtsZ (mt-αFTsZ) with the ability to be targeted to mitochondria inside human cells. Interestingly, the authors found that not only did the mt-αFTsZ protein localize to the mitochondrial matrix before DRP1 bound to the OMM, but mt-αFTsZ also increased mitochondrial fission events in the cell. The authors’ findings led to the discovery of novel proteins that associate with mt-αFtsZ, suggesting the presence of a unique IMM fission machinery.
Key findings:
1. Proteobacterial FtsZ punctae localize to mitochondrial matrix constrictions and induce fission
The authors observed that the human codon-optimized version of Ftsz (mt-αFtsZ) expressed inside cells formed punctae that localized to mitochondrial matrix constrictions. The C-terminus of mt-αFtsZ was essential for its ability to localize to the IMM and induce fission. Using electron microscopy, the authors showed that the expression of mt-αFtsZ inside cells did not affect the ultrastructure of the mitochondrial constrictions. The authors also showed that the expression of full-length mt-αFtsZ induced mitochondrial fission.
2. mt-αFtsZ localizes to mitochondrial matrix constructions before DRP1 is recruited to the OMM
Through live-cell imaging, the authors observed that all fission sites contained mt-αFtsZ, and these punctae distributed to the tips of the daughter mitochondria upon abscission. Additionally, the authors showed that the full-length mt-αFtsZ punctae are recruited to matrix constriction sites before the recruitment of DRP1 on the outer mitochondrial membrane during mitochondrial fission, thus, suggesting that matrix constrictions occur before DRP1-mediated outer mitochondrial membrane scission.
3. mt-αFtsZ localization to the IMM is independent of the replication of the mitochondrial nucleoid
The authors found that the mt-αFtsZ punctae and the mitochondrial nucleoids, for the most part, do not co-localize with each other. To test whether the small co-localizing subset contained replicating nucleoids, the authors labeled actively replicating mtDNAs and found that they also do not colocalize with mt-αFtsZ punctae. Upon inhibiting mtDNA replication using dideoxycytosine (ddC), the nucleoid packing protein localized to the entire matrix instead of just the nucleoids. However, in the presence of ddC, the localization of mt-αFtsZ was unaffected suggesting that mt-αFtsZ localization is independent of nucleoid replication.
4. Four candidate proteins were identified as effectors of inner mitochondrial membrane fission
To identify the players involved in IMM fission, the authors identified the interaction partners of mt-αFtsZ using an immunoprecipitation approach and quantitative mass spectrometry. Using gene ontology analysis, the authors were able to narrow down on five highly enriched mitochondrial inner membrane proteins, namely the mitochondrial serine-threonine phosphatase PGAM5, MTCH1 (mitochondrial carrier homolog 1), FAM210A, the ATP synthase membrane subunit DAPIT (diabetes-associated protein in insulin-sensitive tissue) and SFXN3 (Sideroflexin 3). Four of the five proteins expressed inside cells localized at matrix constrictions and induced mitochondrial fission. However, silencing these proteins did not induce mitochondrial fusion. Thus, the authors identified PGAM5, MTCH1, FAM210A, and SFXN3 as putative effectors of IMM fission.
What I liked about this preprint:
Whenever I have thought about mitochondrial fission, only the ER constriction with actin and DRP1 mediated fission mechanism would come to mind. Therefore, when I came across this preprint which proposed a fission machinery that occurs prior to DRP1-mediated fission, I was immediately curious to know more. Upon finding out that the bacterial fission machinery can induce mitochondrial fission, I was quite excited. The authors have not only alluded to the existence of an inner membrane fission machinery that shares structural features with the bacterial fission machinery, they have also opened doors to further understand the evolutionary past of mitochondria.
References:
- Sprenger, H.-G., & Langer, T. (2019). The Good and the Bad of Mitochondrial Breakups. Trends in Cell Biology, 29(11), 888–900. http://doi.org/https://doi.org/10.1016/j.tcb.2019.08.003
- Wai, T., & Langer, T. (2016). Mitochondrial Dynamics and Metabolic Regulation. Trends in Endocrinology & Metabolism, 27(2), 105–117. http://doi.org/https://doi.org/10.1016/j.tem.2015.12.001
- Martijn, J., Vosseberg, J., Guy, L., Offre, P., & Ettema, T. J. G. (2018). Deep mitochondrial origin outside the sampled alphaproteobacteria. Nature, 557(7703), 101–105.
- Leger, M. M., Petrů, M., Žárský, V., Eme, L., Vlček, Č., Harding, T., et al. (2015). An ancestral bacterial division system is widespread in eukaryotic mitochondria. Proc Natl Acad Sci USA, 112(33), 10239.
- Kraus, F., & Ryan, M. T. (2017). The constriction and scission machineries involved in mitochondrial fission. Journal of Cell Science, 130(18), 2953–2960. http://doi.org/10.1242/jcs.199562
- Szwedziak, P., Wang, Q., Bharat, T. A. M., Tsim, M., & Löwe, J. (2014). Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division. eLife, 3, e04601. http://doi.org/10.7554/eLife.04601
doi: https://doi.org/10.1242/prelights.17106
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
The RNA binding protein HNRNPA2B1 regulates RNA abundance and motor protein activity in neurites
Felipe Del Valle Batalla
Pharyngeal neuronal mechanisms governing sour taste perception in Drosophila melanogaster
Matthew Davies
Feedback regulation by the RhoA-specific GEF ARHGEF17 regulates actomyosin network disassembly
Vibha SINGH
Also in the evolutionary biology category:
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium
Rodrigo Senovilla-Ganzo
Modular control of time and space during vertebrate axis segmentation
AND
Natural genetic variation quantitatively regulates heart rate and dimension
Girish Kale, Jennifer Ann Black
Fetal brain response to maternal inflammation requires microglia
Manuel Lessi
preListscell biology category:
in theBSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
List by | Dey Lab, Amanda Haage |
Also in the evolutionary biology category:
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
List by | preLights peer support |
EMBO | EMBL Symposium: The organism and its environment
This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).
List by | Girish Kale |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
List by | Martin Estermann |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
List by | Alex Eve |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
List by | Ana Dorrego-Rivas |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
List by | Maiko Kitaoka et al. |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
List by | Hiral Shah |
COVID-19 / SARS-CoV-2 preprints
List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic
List by | Dey Lab, Zhang-He Goh |
1
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
List by | Alexa Sadier |