HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE

Tiffany N. Caza; David R. Fernandez; Gergely Talaber; Zachary Oaks; Mark Haas; Michael P. Madaio; Zhi Wei Lai; Gabriella Miklossy; Ram R. Singh; Dmitriy M. Chudakov; Walter Malorni; Frank Middleton; Katalin Banki; Andras Perl

doi:10.1136/annrheumdis-2013-203794

HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE

Tiffany N. Caza, David R. Fernandez, Gergely Talaber, Zachary Oaks, Mark Haas, Michael P. Madaio, Zhi Wei Lai, Gabriella Miklossy, Ram R. Singh, Dmitriy M. Chudakov, Walter Malorni, Frank Middleton, Katalin Banki, Andras Perl

Medicine

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

Abstract

Objective: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupusprone mice.

Original language	English (US)
Pages (from-to)	1888-1897
Number of pages	10
Journal	Annals of the rheumatic diseases
Volume	73
Issue number	10
DOIs	https://doi.org/10.1136/annrheumdis-2013-203794
State	Published - 2014

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology
General Biochemistry, Genetics and Molecular Biology

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Caza, T. N., Fernandez, D. R., Talaber, G., Oaks, Z., Haas, M., Madaio, M. P., Lai, Z. W., Miklossy, G., Singh, R. R., Chudakov, D. M., Malorni, W., Middleton, F., Banki, K., & Perl, A. (2014). HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE. Annals of the rheumatic diseases, 73(10), 1888-1897. https://doi.org/10.1136/annrheumdis-2013-203794

Caza, TN, Fernandez, DR, Talaber, G, Oaks, Z, Haas, M, Madaio, MP, Lai, ZW, Miklossy, G, Singh, RR, Chudakov, DM, Malorni, W, Middleton, F, Banki, K & Perl, A 2014, 'HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE', Annals of the rheumatic diseases, vol. 73, no. 10, pp. 1888-1897. https://doi.org/10.1136/annrheumdis-2013-203794

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title = "HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE",

abstract = "Objective: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupusprone mice.",

author = "Caza, {Tiffany N.} and Fernandez, {David R.} and Gergely Talaber and Zachary Oaks and Mark Haas and Madaio, {Michael P.} and Lai, {Zhi Wei} and Gabriella Miklossy and Singh, {Ram R.} and Chudakov, {Dmitriy M.} and Walter Malorni and Frank Middleton and Katalin Banki and Andras Perl",

year = "2014",

doi = "10.1136/annrheumdis-2013-203794",

language = "English (US)",

volume = "73",

pages = "1888--1897",

journal = "Annals of the rheumatic diseases",

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T1 - HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE

AU - Caza, Tiffany N.

AU - Fernandez, David R.

AU - Talaber, Gergely

AU - Oaks, Zachary

AU - Haas, Mark

AU - Madaio, Michael P.

AU - Lai, Zhi Wei

AU - Miklossy, Gabriella

AU - Singh, Ram R.

AU - Chudakov, Dmitriy M.

AU - Malorni, Walter

AU - Middleton, Frank

AU - Banki, Katalin

AU - Perl, Andras

PY - 2014

Y1 - 2014

N2 - Objective: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupusprone mice.

AB - Objective: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupusprone mice.

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JF - Annals of the rheumatic diseases

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ER -

HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE

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