Necroptosis

&
Relation to PD

Parth Rana
Course OPA-1
Finding in other Research
Content Doubts
 OPA-1
Dynamin GTPase optic atrophy type-1(OPA-1) is a resident of inner
mitochondrial membrane.
It plays a key role in mitochondrial structure and its dynamics.

Dynamin GTPase GTPase

Dynamin acts as a pair of molecular scissors Hydrolase enzymes that convert GTP to GDP.
for newly formed vesicles originating from the GTP helps in protein Signalling and is also an
plasma membrane. energy source.
 Key Roles of OPA-1
Together with Mitofusins
Mitofusins along with OPA-1 help in
maintaining the structural integrity of
the mitochondria and also promote
respiratory efficiency
OPA-1 protein polymerization
Promotes cristae morphogenesis
which helps in facilitating activity of
the respiratory super complexes.Basic
role of respiratory chain
supercomplexes are substrate
channelling, Absence of OPA-1
Results in destabilisation of cristae
structure
Possible activation of apoptotic
pathway
 Necroptosis is a programmed necrosis that

OPA-1 & occurs in neurodegenerative diseases.

PD patients with OPA-1 mutations presented

Parkinson's normal phenotype with only mild

mitochondrial alterations.

Disease It is still quite uncertain of the extent of

OPA-1's effect on mitochondria in neural
cells.
Findings in other Researches
Mitochondrial Dysfunction in PD
Neurotoxins such as 1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP)
and Rotenone activate apoptotic pathways.
Bax and Bak(Apoptotic BCL-2 proteins) are activated downstream to
defective respiratory complex which leads to
Permeabilisation of mitochondrial outer membrane
Cytochrome-c leakage
Caspase Cascade activation
It has been suggested in many researches that degradation of
dopaminergic neurons is not done exclusively by apoptosis, but by other
cell deaths such as Necroptosis, Autophagy and many more.
 Doubts
Pharmacological Inhibition of Necroptosis Protects from Dopaminergic
Neuronal Cell Death in Parkinson’s Disease Models suggested experiment
types which included working on iPSC cells.