Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

Mitochondrial DNA Quantity and Relative Abundance of “Common Deletion” Mutation in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy

Version 1 : Received: 31 January 2024 / Approved: 1 February 2024 / Online: 1 February 2024 (14:09:37 CET)

How to cite: Boustani, A.; Andalibi, M.S.; Pérez-Santiago, J.; Mehta, S.; Ellis, R.J.; Fields, J.A. Mitochondrial DNA Quantity and Relative Abundance of “Common Deletion” Mutation in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy. Preprints 2024, 2024020060. https://doi.org/10.20944/preprints202402.0060.v1 Boustani, A.; Andalibi, M.S.; Pérez-Santiago, J.; Mehta, S.; Ellis, R.J.; Fields, J.A. Mitochondrial DNA Quantity and Relative Abundance of “Common Deletion” Mutation in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy. Preprints 2024, 2024020060. https://doi.org/10.20944/preprints202402.0060.v1

Abstract

Background: Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ART) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. Methods: This study investigated mtDNA, mt fission and fusion protein, and mt electron transport chain protein changes in the dorsal root ganglion (DRG) and sural nerve (SuN) from 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction (ddPCR) measured mtDNA quantity and the common deletion (CD) in isolated DNA. Results: We found lower mtDNA copy numbers in DSP+ donors. SuN exhibited a higher proportion of mtDNA CD than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in DRG of DSP+ compared to DSP- donors, particularly complex I. Conclusion: These findings suggest reduced mtDNA quantity and increased CD abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Keywords

DSP; Distal Symmetric Polyneuropathy; mtDNA; Common Deletion mutation

Subject

Biology and Life Sciences, Neuroscience and Neurology

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