Fis1 is required for the development of the dendritic mitochondrial network in pyramidal cortical neurons
Posted on: 11 February 2025 , updated on: 12 February 2025
Preprint posted on 7 January 2025
Fis1 unexpectedly regulates dendritic mitochondrial dynamics by promoting fission/fusion balance and motility, impacting neuronal function and connectivity.
Selected by Felipe Del Valle BatallaCategories: cell biology, neuroscience
Background
Neurons are highly specialized and polarized cells, with distinct compartments: dendrites (signal receivers), axons (signal transmitters), and the soma (cell body). Each compartment has unique energy and signaling demands, supported by mitochondria.
In dendrites, mitochondria form elongated, interconnected networks to meet the high energy and calcium-buffering demands essential for neuronal signaling. Meanwhile, in axons, mitochondria are smaller and found particularly at energy-intensive sites like presynaptic terminals. These variations are critical for neuronal function, thus, disruptions in mitochondrial dynamics can lead to neurodegeneration and developmental disorders like Alzheimer’s disease.
Mitochondrial shape and distribution are maintained by a balance of fission (division into smaller units) and fusion (merging into networks), regulated by specific proteins. In this work, Strucinska et al , focus on Fis1, a protein involved in mitochondrial fission, particularly in dendrites. While the role of other canonical proteins like Mff (mitochondrial fission factor) in axonal mitochondrial fission is well-known (1), the role of Fis1 in dendrites remains less understood. Since Mff knockout mainly affects axonal mitochondria, this research investigates how Fis1 regulates dendritic mitochondrial dynamics, essential for neuronal health.
Key findings
Loss of Fis1 promotes compartment-specific changes in mithochondrial morphology and dynamics
Initially, Strucinska and cols. hypothesized that Fis1 would promote mitochondrial division in dendrites, but they observed the opposite effect when Fis1 activity was reduced. Specifically, Fis1 knockdown led to shorter dendritic mitochondria (Fig. 1), without affecting axonal mitochondria size. This suggests that Fis1’s role in mitochondrial morphology is compartment-specific, primarily influencing dendrites.
To explore the underlying mechanisms, the researchers examined mitochondrial dynamics in dendrites following Fis1 knockdown. They found a significant increase in mitochondrial motility, as well as a higher frequency of both fission and fusion events (Fig. 2). Notably, mitochondrial fission events doubled, while fusion rates were modestly increased. Together, these findings highlight the unexpected role of mitochondrial dynamics and morphology in distinct neuronal compartments, challenging the view that Fis1 is a universal promoter of mitochondrial fission.
Functional Impact of Fis1 Loss on Mitochondria: membrane potential and calcium handling
Using TMRM to measure mitochondrial membrane potential, the researchers revealed a reduction in potential following Fis1 knockdown (Fig. 3). This proposes that Fis1 is essential for maintaining mitochondrial membrane integrity, and its loss leads to compromised bioenergetics. Reduced membrane potential can have wide-reaching effects on cellular metabolism and energy production, which are critical for sustaining neuronal activity.
In addition to mitochondrial dysfunction, the study examined the effects of Fis1 loss on neuronal calcium handling. Results show that Fis1 knockdown led to significantly elevated resting calcium levels in neurons, likely due to impaired mitochondrial calcium uptake (Fig. 4). The reduction in endoplasmic reticulum calcium uptake further supports this conclusion, indicating that compromised mitochondrial function disrupts calcium homeostasis. Disrupted calcium regulation can have downstream effects on cellular signaling, synaptic plasticity, and overall neuronal health, underscoring the interconnectedness of mitochondrial function and neuronal signaling.
Impact on dendritic development and synaptic connectivity
Finally, the authors explored how altered calcium signaling and mitochondrial dynamics affected dendritic development. They performed Scholl analysis and found that Fis1 knockdown resulted in increased dendritic branching. However, despite the increased branching, spine density was reduced in vivo, which can result in an alteration in synaptic connectivity (Fig. 5). These findings underscore the importance of Fis1 in regulating not only mitochondrial function and dynamics but also dendritic structure and synaptic connectivity.
Why I think this preprint is relevant
This study is important because it shows a compartment-specific and unexpected role for Fis1 in regulating dendritic mitochondrial morphology and function. The finding that reducing Fis1 activity leads to shorter, rather than longer, dendritic mitochondria is rather surprising and suggests a more complex role for Fis1 in mitochondrial dynamics than previously thought. This new understanding of Fis1’s role in neuronal mitochondria could have implications for considering how conventional targets of developmental disorders and neurodegeneration are treated.
Future directions and questions for the authors
Personally, I think that the following studies should explore the exact mechanisms through which Fis1 regulates dendritic mitochondrial morphology. It would be important to determine if Fis1 interacts with other fusion factors such as Drp1 receptors (Mff or Mief1/2), if it recruits non-active forms of Drp1 to dendritic mitochondria, or if it interacts with fusion machinery.
How does the loss of Fis1 alter the mitochondrial anchoring system in dendrites? Further, does Fis1 play a role in the formation or dynamics of mitochondrial-ER contact sites?
It would also be interesting to investigate whether Fis1 plays a role, directly or indirectly with Mff, in dendritic calcium-dependent fission and to determine if the changes observed are sufficient to reduce mitochondrial dynamics in a manner that favors a pro-fusion phenotype.
References
(1) Lewis, T.L., Jr., et al., MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nat Commun, 2018. 9(1): p. 5008.
doi: https://doi.org/10.1242/prelights.39617
Read preprintSign up to customise the site to your preferences and to receive alerts
Register hereAlso in the cell biology category:
Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche
Simon Cleary

Mechanical stresses govern myoblast fusion and myotube growth
Vibha SINGH, Prasanna Padmanaban

Polystyrene nanoplastics promote neurodegeneration by catalyzing TDP43 hyperphosphorylation
Manuel Lessi

Also in the neuroscience category:
A zebrafish circuit for behavioral credit assignment
Muhammed Sinan Malik

Fis1 is required for the development of the dendritic mitochondrial network in pyramidal cortical neurons
Felipe Del Valle Batalla

Levetiracetam prevents Aβ42 production through SV2a-dependent modulation of App processing in Alzheimer’s disease models
Jawdat Sandakly

preLists in the cell biology category:
February in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry and cell metabolism 2) cell organelles and organisation 3) cell signalling, migration and mechanosensing
List by | Barbora Knotkova et al. |
Community-driven preList – Immunology
In this community-driven preList, a group of preLighters, with expertise in different areas of immunology have worked together to create this preprint reading list.
List by | Felipe Del Valle Batalla et al. |
January in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry/metabolism 2) cell migration 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics/gene expression
List by | Barbora Knotkova et al. |
December in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) cell cycle and division 2) cell migration and cytoskeleton 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics/gene expression
List by | Matthew Davies et al. |
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
List by | Felipe Del Valle Batalla et al. |
BSCB-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 neuroscience category:
2024 Hypothalamus GRC
This 2024 Hypothalamus GRC (Gordon Research Conference) preList offers an overview of cutting-edge research focused on the hypothalamus, a critical brain region involved in regulating homeostasis, behavior, and neuroendocrine functions. The studies included cover a range of topics, including neural circuits, molecular mechanisms, and the role of the hypothalamus in health and disease. This collection highlights some of the latest advances in understanding hypothalamic function, with potential implications for treating disorders such as obesity, stress, and metabolic diseases.
List by | Nathalie Krauth |
‘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 |
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 |
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 |
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. |
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 |
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 |
Young Embryologist Network Conference 2019
Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London
List by | Alex Eve |