MicroBio Pharmaceuticals and Pharmacology | Online ISSN 2209-2161
RESEARCH ARTICLE   (Open Access)

Mitochondrial Targeted AFG3 Abolishment Triggers Higher Mitochondrial Membrane Potential (ΔΨm) in Young Yeast

Ashfaqul Muid Khandakera*, Ahmet Kocb

+ Author Affiliations

Microbial Bioactives 3(1) 119-124 https://doi.org/10.25163/microbbioacts.31003A0713270620

Submitted: 07 April 2020  Revised: 11 June 2020  Published: 27 June 2020 

Molecular insight into the human genetic disease, spastic paraplegia through yeast model

Abstract


Yeast AFG3 gene is homologous to human AFG3L2 and SPG7 genes whose encoded proteins interact with each other on the mitochondrial inner membrane to form the m-AAA metalloproteinase complex. Mutations associated with the gene SPG7 cause autosomal recessive disease spastic paraplegia and a type of ataxia in human but the mitochondrial activity in terms of mitochondrial membrane potential was not investigated previously. In our earlier study, we characterized AFG3 gene deletion yeast mutant and found this mutant gained altered mitochondrial morphology and functions such as mitochondrial aggregation, absence of ROS, less ATP etc. In this current study, we further investigated the effect of AFG3 deletion on mitochondrial health and activation in yeast models. To do so, the rate of oxygen consumption was measured and found that afg3Δ consumed less amount of oxygen compared to wild type (WT). In addition, mitochondrial membrane potential was measured and found that young afg3Δ gained significantly higher membrane potential (doubled) compared to WT. As Afg3 degrades unassembled or unfolded proteins, we also analyzed mitochondrial unfolded protein response (UPRmt) signal and found inactivated indicating mitochondrial proteostatic balance was any how managed and augmentation of ΔΨm may play role here. Physical interaction with AFG3 were sorted out and classified in order to find out how the interactive network may hamper due to abolishment of the Afg3 protein function. Thus this investigation in yeast (Saccharomyces cerevisiae) model may provide additional information in the study of human spastic paraplegia.

Keywords: Mitochondrial membrane potential (ΔΨm), Oxygen consumption, AFG3, mitochondrial unfolded protein response (UPRmt) and human spastic paraplegia

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