Demers-Lamarche, Julie

Germain, Marc

Ouelette, Mathieu

Todkar, Kiran

Vishwa, Anjali

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Anja l i  Vishwa 1 ,2 ,3 ,  K i ran  Todkar,  Ju l ie  Demers -Lamarche ,  Math ieu  Ouel le t (Ce l l  l ines ) ,  Marc  Germain1 .  Dépar tement de  Bio log ie médica le e t  Groupe  de  Recherche  en Signa l i sa t ion  Cel lu la i re ,  UQTR2.  Cen t re  d 'exce l lence en recherche  su r  l es  malad ies  o rphe l ines - Fonda t ion Cour to i s  (CERMO -FC)3 .  Réseau In te rsec to r ie l de  recherche  en  San té  de  l ’Univers i t é du  Québec  (RISUQ )IntroductionMitochondrial dysfunction cause aggregation of early endosome in the perinuclear region in mouse embryonic fibroblast (MEFs)Figure 1: Impact of mitochondria functional loss in early endosome structure. a) Cells were tagged with Rab5 (early endosome)and DAPI (nucleus). The boxed areas indicate cells with aggregated early endosome in the perinuclear region. b) Quantification of early endosomeaggregation.aa bMitochondrial dysfunction cause aggregation of early endosome in the perinuclear region in patient cells with a Drp1 mutationDAPI: Nucleus Rab5: Early endosomeControlDrp1 mutant050100% of cell with Rab5 aggregateFigure 2: Impact of mitochondria functional loss in early endosome structure in primary fibroblasts mutant for the mitochondrial fissionprotein DRP1 a) Control and DRP1 mutant cells were tagged with Rab5 (early endosome) and DAPI (nucleus). The boxed areas indicate cellswith aggregated early endosome in the perinuclear region b) Quantification of early endosome aggregation.3. Actin plays a role in driving early endosomal aggregation in perinuclear regionWT MEFs OPA1 KO MEFsFigure 3: Early endosomes colocalise with actin patches in cells with dysfunctional mitochondria:WT and OPA1 KO MEFs were tagged with Rab5 (early endosome) and phalloidin (actin). Line scans (bottom) showing colocalization between Rab5 and phalloidin were performed in Fiji.​bMethodologyHypothesisMitochondrial impairment affects the endocytic pathway• Mitochondria play a key role in the regulation ofmetabolism, cell signalling, apoptosis and immunity, whilemutations affecting mitochondrial function generally causeneurological or muscular pathologies.• To exert their roles, mitochondria interact with differentorganelles. Among the organelles interacting withmitochondria, endosomes are required for the delivery ofextracellular and cytoplasmic material to lysosomes fordegradation.• In this context, the interaction between endosomes andmitochondria has been proposed to promote the traffickingof endocytosed material and endosomal maturation, but theunderlying mechanisms remain elusive.Hypothesis1.bResults2.DAPI: Nucleus Rab5: Early endosomeDistance (μm)Signal intensityRab5/Phalloidin PhalloidinRab5aConclusion Cell with healthy mitochondria Cell with dysfunctional mitochondriaMitochondrial dysfunction leads to the aggregation of early endosome in the perinuclear region. Future experiments • We will determine the consequence of mitochondrial dysfunction on early endosome function by measuring dextran and transferrin uptake.• To study the mechanism of the early endosome aggregation in cells with mitochondrial dysfunction, the association between the two organelles will be analysed.References 1. Demers-Lamarche, J., Guillebaud, G., Tlili, M.,Todkar, K., Bélanger, N., Grondin, M., Nguyen,A.P., Michel, J. and Germain, M., 2016. Loss ofmitochondrial function impairs lysosomes. Journalof biological chemistry, 291(19), pp.10263-102762. Paul, S., Saha, D., & Binukumar, B. K. (2021).Mitochondrial Dysfunction and Mitophagy CloselyCooperate in Neurological Deficits Associatedwith Alzheimer’s Disease and Type 2Diabetes. Molecular Neurobiology, 1-15.***Structural impairment in the early endosome in mitochondrial dysfunctioned cell could affect the endocytic pathwayEarly endosomeRab5/Phalloidin PhalloidinRab5

Mitochondrial dysfunction : the endocytic pathway connection

https://depot-e.uqtr.ca/id/eprint/10163/1/ANJALI%20JAYKUMAR%20VISHWAKARMA.pdf

Mitochondrial dysfunction : the endocytic pathway connection

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