Authors :
Mohan Kumar BS; Mahaboob Basha P
Volume/Issue :
Volume 5 - 2020, Issue 6 - June
Google Scholar :
http://bitly.ws/9nMw
Scribd :
https://bit.ly/2YOHGj3
DOI :
10.38124/IJISRT20JUN323
Abstract :
Ca2+ sequestration and its homeostasis is
disrupted when mitochondrial membrane permeabilises
to form a large opening - the mitochondrial
permeability transition pore (MPTP). The MPTP
formation is common during aging and age related
pathologies, activating cell death pathways to avoid
unhealthy consequences and malignancies in the brain
tissue. Several studies have identified the participation
of Cyclophilin-D (Cyp-D) and adenine nucleotide
translocase(ANT) in forming MPTP. However, Ca2+ is
known to participate significantly in MPTP induction,
although its concentration and time dependent
permeabilization mechanisms are still elusive.
In this work, we have focused on the contribution
of Ca2+ participation, its concentration and time taken
to permeabilze the mitochondrial inner membrane as a
measure of light scattering at 540 ηM. We have
observed that MPTP formation is increased in
mitochondria isolated from aged rats in comparison to
young adult and neonatal rats. The cyclosporin A
application blocks the cyclophilin interaction thus
avoiding MPTP formation confirming the crucial role of
Ca2+ inducted MPTP opening. A 100 µM Ca2+
incubation for 15 minutes allowed the 50% probability
of formation of MPTP in mitochondria isolated from all
age groups. Thus, alleviating its role in aging and
neurodegeneration.
Keywords :
Mitochondria;Ca2+ ;Aging;Mitochondrial Permeability Transition Pore (MPTP).
Ca2+ sequestration and its homeostasis is
disrupted when mitochondrial membrane permeabilises
to form a large opening - the mitochondrial
permeability transition pore (MPTP). The MPTP
formation is common during aging and age related
pathologies, activating cell death pathways to avoid
unhealthy consequences and malignancies in the brain
tissue. Several studies have identified the participation
of Cyclophilin-D (Cyp-D) and adenine nucleotide
translocase(ANT) in forming MPTP. However, Ca2+ is
known to participate significantly in MPTP induction,
although its concentration and time dependent
permeabilization mechanisms are still elusive.
In this work, we have focused on the contribution
of Ca2+ participation, its concentration and time taken
to permeabilze the mitochondrial inner membrane as a
measure of light scattering at 540 ηM. We have
observed that MPTP formation is increased in
mitochondria isolated from aged rats in comparison to
young adult and neonatal rats. The cyclosporin A
application blocks the cyclophilin interaction thus
avoiding MPTP formation confirming the crucial role of
Ca2+ inducted MPTP opening. A 100 µM Ca2+
incubation for 15 minutes allowed the 50% probability
of formation of MPTP in mitochondria isolated from all
age groups. Thus, alleviating its role in aging and
neurodegeneration.
Keywords :
Mitochondria;Ca2+ ;Aging;Mitochondrial Permeability Transition Pore (MPTP).
