Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

Kerry Blair; Raquel Martinez Serra; Philippe Gosset; Sandra Martin Guerrero; Gabor Morotz; Joe Atherton; Jackie Mitchell; Andrea Markovinovic; Christopher Miller

Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

Kerry Blair, Raquel Martinez Serra, Philippe Gosset, Sandra Martin Guerrero, Gabor Morotz, Joe Atherton, Jackie Mitchell, Andrea Markovinovic, Christopher Miller^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.

Original language	English
Article number	10.1186/s40478-025-01964-7
Journal	Acta Neuropathologica Communications
Publication status	Unpublished - 25 Feb 2025

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@article{f5318c4ca2134c3da70a608306026301,

title = "Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases",

abstract = "Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer{\textquoteright}s disease, Parkinson{\textquoteright}s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer{\textquoteright}s disease, Parkinson{\textquoteright}s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.",

author = "Kerry Blair and {Martinez Serra}, Raquel and Philippe Gosset and {Martin Guerrero}, Sandra and Gabor Morotz and Joe Atherton and Jackie Mitchell and Andrea Markovinovic and Christopher Miller",

year = "2025",

month = feb,

day = "25",

language = "English",

journal = "Acta Neuropathologica Communications",

issn = "2051-5960",

publisher = "BioMed Central",

}

TY - JOUR

T1 - Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

AU - Blair, Kerry

AU - Martinez Serra, Raquel

AU - Gosset, Philippe

AU - Martin Guerrero, Sandra

AU - Morotz, Gabor

AU - Atherton, Joe

AU - Mitchell, Jackie

AU - Markovinovic, Andrea

AU - Miller, Christopher

PY - 2025/2/25

Y1 - 2025/2/25

N2 - Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.

AB - Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.

M3 - Review article

SN - 2051-5960

JO - Acta Neuropathologica Communications

JF - Acta Neuropathologica Communications

M1 - 10.1186/s40478-025-01964-7

ER -

Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

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