Over‐expression of an S‐adenosylmethionine‐dependent methyltransferase leads to an extended lifespan of Podospora anserina without impairments in vital functions

Abstract

SummaryPaMTH1, a putative methyltransferase previously described to increase in abundance in total protein extracts during aging of Podospora anserina is demonstrated to accumulate in the mitochondrial cell fraction of senescent cultures. The protein is localized in the mitochondrial matrix and displays a methyltransferase activity utilizing flavonoids as substrates. Constitutive over-expression of PaMth1 in P. anserina results in a reduced carbonylation of proteins and an extended lifespan without impairing vital functions suggesting a protecting role of PaMTH1 against oxidative stress.

Unmasking a temperature-dependent effect of theP. anserinai-AAA protease on aging and development

“…The monomer of complex V (V M ) and the dimer ROS generation via the overexpression of a gene coding for a mitochondrial methyltransferase (PaMTH1) lowers the timedependent accumulation of damaged mitochondrial proteins and results in increased stress resistance and healthspan of transgenic strains of P. anserina. 43 Consistently, the deletion of PaMth1 was found to lead to accelerated aging. 44 Recently, similar effects were obtained when the abundance of components of the mitochondrial protein quality control system were changed by different specific genetic manipulations of P. anserina.…”

“…The generated PCR product was digested with KpnI and EcoRV and cloned into the KpnIEcoRVdigested plasmid pKO7. 43 The nucleotide sequence was verified by sequencing (SRD GmbH), and the vector pPaIap_rev was transformed into P. anserina protoplasts of the strain ΔPaIap. The strains containing the ORF of PaIap were selected by hygromycin B (Hyg) resistance.…”

Cyclophilin D links programmed cell death and organismal aging in Podospora anserina

“…Mitochondria of P. anserina cultures were isolated by differential centrifugation and purified using a 20-50% discontinuous sucrose gradient as described previously (Kunstmann & Osiewacz, 2008).…”

“…Total protein was extracted as described previously (Kunstmann & Osiewacz, 2008). Hundred micrograms of total protein were separated on a native 8.5% polyacrylamide gel and stained using nitroblue tetrazolium (NBT), riboflavin and N,N,N',N'-tetramethylethylenediamine .…”

Unopposed mitochondrial fission leads to severe lifespan shortening

“…[1][2][3][4][5][6] Several pathways are dedicated to ensure the uncompromised ability of mitochondria to cope with changing cellular demands. [7][8][9][10][11][12] One pathway that recently gained special interest is the regulation and execution of mitochondrial fusion and fission. These opposing events are normally balanced and, in addition to further accessory proteins, under the tight control of large dynamin-related GTPases.…”