Methane produced from methanogenesis in archaea may be a promising source of renewable energy as methanogens are the primary producers of biogenic methane. However, methanogens are anaerobic and experience transient oxygen exposure in their environment, leading to degradation of proteins involved in methanogenesis pathways. Elucidating the oxidative stress response mechanisms in methanogens may lead to the development of more oxygen-tolerant strains with robust methanogenesis capabilities in bioreactors for production of methane as a renewable energy source. MsvR is a redox-sensitive transcription regulator exclusively found in methanogens. It was initially identified in M. thermautotrophicus as a regulator of the fpaA-rlp-rub operon, which is implicated in the oxidative stress response. The MsvR homolog in M. acetivorans (MaMsvR) was found to have ten cysteine residues, three of which are conserved in MsvR from M. thermautotrophicus. This lead to the substitutional analysis of each cysteine in MaMsvR that implicated seven cysteines (C63, C89, C148, C175, C206, C232 and C240) in redox sensing and/or conformational change affecting MaMsvR binding to its promoter (Ma PmsvR). RNA-seq was utilized for preliminary analysis of the MaMsvR regulon and it was found that MaMsvR directly or indirectly regulates genes encoding function in methanogenesis, signal transduction, transcription regulation and various other cellular functions. The data suggests MaMsvR is involved in regulatory hierarchies that modulate central metabolism and that regulation may be redox-dependent.